A terminal section of a chromosome which has a specialized structure and which is involved in chromosomal replication and stability. Its length is believed to be a few hundred base pairs.
Maintenance of TELOMERE length. During DNA REPLICATION, chromosome ends loose some of their telomere sequence (TELOMERE SHORTENING.) Various cellular mechanism are involved in repairing, extending, and recapping the telomere ends.
An essential ribonucleoprotein reverse transcriptase that adds telomeric DNA to the ends of eukaryotic CHROMOSOMES.
Proteins that specifically bind to TELOMERES. Proteins in this class include those that perform functions such as telomere capping, telomere maintenance and telomere stabilization.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
The decrease in the cell's ability to proliferate with the passing of time. Each cell is programmed for a certain number of cell divisions and at the end of that time proliferation halts. The cell enters a quiescent state after which it experiences CELL DEATH via the process of APOPTOSIS.
A type of IN SITU HYBRIDIZATION in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei.
A predominantly X-linked recessive syndrome characterized by a triad of reticular skin pigmentation, nail dystrophy and leukoplakia of mucous membranes. Oral and dental abnormalities may also be present. Complications are a predisposition to malignancy and bone marrow involvement with pancytopenia. (from Int J Paediatr Dent 2000 Dec;10(4):328-34) The X-linked form is also known as Zinsser-Cole-Engman syndrome and involves the gene which encodes a highly conserved protein called dyskerin.
A group of telomere associated proteins that interact with TRF1 PROTEIN, contain ANKYRIN REPEATS and have poly(ADP-ribose) polymerase activity.
Higher-order DNA and RNA structures formed from guanine-rich sequences. They are formed around a core of at least 2 stacked tetrads of hydrogen-bonded GUANINE bases. They can be formed from one two or four separate strands of DNA (or RNA) and can display a wide variety of topologies, which are a consequence of various combinations of strand direction, length, and sequence. (From Nucleic Acids Res. 2006;34(19):5402-15)
A genus of ciliate protozoa having a unique cursorial type of locomotion.
An increased tendency to acquire CHROMOSOME ABERRATIONS when various processes involved in chromosome replication, repair, or segregation are dysfunctional.
Structures within the nucleus of fungal cells consisting of or containing DNA, which carry genetic information essential to the cell.
White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Injuries to DNA that introduce deviations from its normal, intact structure and which may, if left unrepaired, result in a MUTATION or a block of DNA REPLICATION. These deviations may be caused by physical or chemical agents and occur by natural or unnatural, introduced circumstances. They include the introduction of illegitimate bases during replication or by deamination or other modification of bases; the loss of a base from the DNA backbone leaving an abasic site; single-strand breaks; double strand breaks; and intrastrand (PYRIMIDINE DIMERS) or interstrand crosslinking. Damage can often be repaired (DNA REPAIR). If the damage is extensive, it can induce APOPTOSIS.
An increased tendency of the GENOME to acquire MUTATIONS when various processes involved in maintaining and replicating the genome are dysfunctional.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
In a prokaryotic cell or in the nucleus of a eukaryotic cell, a structure consisting of or containing DNA which carries the genetic information essential to the cell. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The gradual irreversible changes in structure and function of an organism that occur as a result of the passage of time.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
A genus of ciliate protozoa having a dorsoventrally flattened body with widely spaced rows of short bristle-like cilia on the dorsal surface.
A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A set of nuclear proteins in SACCHAROMYCES CEREVISIAE that are required for the transcriptional repression of the silent mating type loci. They mediate the formation of silenced CHROMATIN and repress both transcription and recombination at other loci as well. They are comprised of 4 non-homologous, interacting proteins, Sir1p, Sir2p, Sir3p, and Sir4p. Sir2p, an NAD-dependent HISTONE DEACETYLASE, is the founding member of the family of SIRTUINS.
Deoxyribonucleic acid that makes up the genetic material of fungi.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A family of enzymes that catalyze the exonucleolytic cleavage of DNA. It includes members of the class EC 3.1.11 that produce 5'-phosphomonoesters as cleavage products.
Very long DNA molecules and associated proteins, HISTONES, and non-histone chromosomal proteins (CHROMOSOMAL PROTEINS, NON-HISTONE). Normally 46 chromosomes, including two sex chromosomes are found in the nucleus of human cells. They carry the hereditary information of the individual.
Immunologically detectable substances found in the CELL NUCLEUS.
Abnormal number or structure of chromosomes. Chromosome aberrations may result in CHROMOSOME DISORDERS.
Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.
Changes in the organism associated with senescence, occurring at an accelerated rate.
The process by which a DNA molecule is duplicated.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A DNA-binding protein that mediates DNA REPAIR of double strand breaks, and HOMOLOGOUS RECOMBINATION.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
A family of structurally-related DNA helicases that play an essential role in the maintenance of genome integrity. RecQ helicases were originally discovered in E COLI and are highly conserved across both prokaryotic and eukaryotic organisms. Genetic mutations that result in loss of RecQ helicase activity gives rise to disorders that are associated with CANCER predisposition and premature aging.
The loss of some TELOMERE sequence during DNA REPLICATION of the first several base pairs of a linear DNA molecule; or from DNA DAMAGE. Cells have various mechanisms to restore length (TELOMERE HOMEOSTASIS.) Telomere shortening is involved in the progression of CELL AGING.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
An energy dependent process following the crosslinking of B CELL ANTIGEN RECEPTORS by multivalent ligands (bivalent anti-antibodies, LECTINS or ANTIGENS), on the B-cell surface. The crosslinked ligand-antigen receptor complexes collect in patches which flow to and aggregate at one pole of the cell to form a large mass - the cap. The caps may then be endocytosed or shed into the environment.

Analysis of genomic integrity and p53-dependent G1 checkpoint in telomerase-induced extended-life-span human fibroblasts. (1/4834)

Life span determination in normal human cells may be regulated by nucleoprotein structures called telomeres, the physical ends of eukaryotic chromosomes. Telomeres have been shown to be essential for chromosome stability and function and to shorten with each cell division in normal human cells in culture and with age in vivo. Reversal of telomere shortening by the forced expression of telomerase in normal cells has been shown to elongate telomeres and extend the replicative life span (H. Vaziri and S. Benchimol, Curr. Biol. 8:279-282, 1998; A. G. Bodnar et al., Science 279:349-352, 1998). Extension of the life span as a consequence of the functional inactivation of p53 is frequently associated with loss of genomic stability. Analysis of telomerase-induced extended-life-span fibroblast (TIELF) cells by G banding and spectral karyotyping indicated that forced extension of the life span by telomerase led to the transient formation of aberrant structures, which were subsequently resolved in higher passages. However, the p53-dependent G1 checkpoint was intact as assessed by functional activation of p53 protein in response to ionizing radiation and subsequent p53-mediated induction of p21(Waf1/Cip1/Sdi1). TIELF cells were not tumorigenic and had a normal DNA strand break rejoining activity and normal radiosensitivity in response to ionizing radiation.  (+info)

A telomere-independent senescence mechanism is the sole barrier to Syrian hamster cell immortalization. (2/4834)

Reactivation of telomerase and stabilization of telomeres occur simultaneously during human cell immortalization in vitro and the vast majority of human cancers possess high levels of telomerase activity. Telomerase repression in human somatic cells may therefore have evolved as a powerful resistance mechanism against immortalization, clonal evolution and malignant progression. The comparative ease with which rodent cells immortalize in vitro suggests that they have less stringent controls over replicative senescence than human cells. Here, we report that Syrian hamster dermal fibroblasts possess substantial levels of telomerase activity throughout their culture life-span, even after growth arrest in senescence. In our studies, telomerase was also detected in uncultured newborn hamster skin, in several adult tissues, and in cultured fibroblasts induced to enter the post-mitotic state irreversibly by serum withdrawal. Transfection of near-senescent dermal fibroblasts with a selectable plasmid vector expressing the SV40 T-antigen gene resulted in high-frequency single-step immortalization without the crisis typically observed during the immortalization of human cells. Collectively, these data provide an explanation for the increased susceptibility of rodent cells to immortalization (and malignant transformation) compared with their human equivalents, and provide evidence for a novel, growth factor-sensitive, mammalian senescence mechanism unrelated to telomere maintenance.  (+info)

Telomeric repeats on small polydisperse circular DNA (spcDNA) and genomic instability. (3/4834)

Small polydisperse circular DNA (spcDNA) is a heterogeneous population of extrachromosomal circular molecules present in a large variety of eukaryotic cells. Elevated amounts of total spcDNA are related to endogenous and induced genomic instability in rodent and human cells. We suggested spcDNA as a novel marker for genomic instability, and speculated that spcDNA might serve as a mutator. In this study, we examine the presence of telomeric sequences on spcDNA. We report for the first time the appearance of telomeric repeats in spcDNA molecules (tel-spcDNA) in rodent and human cells. Restriction enzyme analysis indicates that tel-spcDNA molecules harbor mostly, if not exclusively, telomeric repeats. In rodent cells, tel-spcDNA levels are higher in transformed than in normal cells and are enhanced by treatment with carcinogen. Tel-spcDNA is also detected in some human tumors and cell lines, but not in others. We suggest, that its levels in human cells may be primarily related to the amount of the chromosomal telomeric sequences. Tel-spcDNA may serve as a unique mutator, through specific mechanisms related to the telomeric repeats, which distinguish it from the total heterogeneous spcDNA population. It may affect telomere dynamics and genomic instability by clastogenic events, alterations of telomere size and sequestration of telomeric proteins.  (+info)

p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. (4/4834)

Although broken chromosomes can induce apoptosis, natural chromosome ends (telomeres) do not trigger this response. It is shown that this suppression of apoptosis involves the telomeric-repeat binding factor 2 (TRF2). Inhibition of TRF2 resulted in apoptosis in a subset of mammalian cell types. The response was mediated by p53 and the ATM (ataxia telangiectasia mutated) kinase, consistent with activation of a DNA damage checkpoint. Apoptosis was not due to rupture of dicentric chromosomes formed by end-to-end fusion, indicating that telomeres lacking TRF2 directly signal apoptosis, possibly because they resemble damaged DNA. Thus, in some cells, telomere shortening may signal cell death rather than senescence.  (+info)

Telomere length dynamics and chromosomal instability in cells derived from telomerase null mice. (5/4834)

To study the effect of continued telomere shortening on chromosome stability, we have analyzed the telomere length of two individual chromosomes (chromosomes 2 and 11) in fibroblasts derived from wild-type mice and from mice lacking the mouse telomerase RNA (mTER) gene using quantitative fluorescence in situ hybridization. Telomere length at both chromosomes decreased with increasing generations of mTER-/- mice. At the 6th mouse generation, this telomere shortening resulted in significantly shorter chromosome 2 telomeres than the average telomere length of all chromosomes. Interestingly, the most frequent fusions found in mTER-/- cells were homologous fusions involving chromosome 2. Immortal cultures derived from the primary mTER-/- cells showed a dramatic accumulation of fusions and translocations, revealing that continued growth in the absence of telomerase is a potent inducer of chromosomal instability. Chromosomes 2 and 11 were frequently involved in these abnormalities suggesting that, in the absence of telomerase, chromosomal instability is determined in part by chromosome-specific telomere length. At various points during the growth of the immortal mTER-/- cells, telomere length was stabilized in a chromosome-specific man-ner. This telomere-maintenance in the absence of telomerase could provide the basis for the ability of mTER-/- cells to grow indefinitely and form tumors.  (+info)

Telomere loss in somatic cells of Drosophila causes cell cycle arrest and apoptosis. (6/4834)

Checkpoint mechanisms that respond to DNA damage in the mitotic cell cycle are necessary to maintain the fidelity of chromosome transmission. These mechanisms must be able to distinguish the normal telomeres of linear chromosomes from double-strand break damage. However, on several occasions, Drosophila chromosomes that lack their normal telomeric DNA have been recovered, raising the issue of whether Drosophila is able to distinguish telomeric termini from nontelomeric breaks. We used site-specific recombination on a dispensable chromosome to induce the formation of a dicentric chromosome and an acentric, telomere-bearing, chromosome fragment in somatic cells of Drosophila melanogaster. The acentric fragment is lost when cells divide and the dicentric breaks, transmitting a chromosome that has lost a telomere to each daughter cell. In the eye imaginal disc, cells with a newly broken chromosome initially experience mitotic arrest and then undergo apoptosis when cells are induced to divide as the eye differentiates. Therefore, Drosophila cells can detect and respond to a single broken chromosome. It follows that transmissible chromosomes lacking normal telomeric DNA nonetheless must possess functional telomeres. We conclude that Drosophila telomeres can be established and maintained by a mechanism that does not rely on the terminal DNA sequence.  (+info)

Telomere shortening in mTR-/- embryos is associated with failure to close the neural tube. (7/4834)

Mice genetically deficient for the telomerase RNA (mTR) can be propagated for only a limited number of generations. In particular, mTR-/- mice of a mixed C57BL6/129Sv genetic background are infertile at the sixth generation and show serious hematopoietic defects. Here, we show that a percentage of mTR-/- embryos do not develop normally and fail to close the neural tube, preferentially at the forebrain and midbrain. The penetrance of this defect increases with the generation number, with 30% of the mTR-/- embryos from the fifth generation showing the phenotype. Moreover, mTR-/- kindreds in a pure C57BL6 background are only viable up to the fourth generation and also show defects in the closing of the neural tube. Cells derived from mTR-/- embryos that fail to close the neural tube have significantly shorter telomeres and decreased viability than their mTR-/- littermates with a closed neural tube, suggesting that the neural tube defect is a consequence of the loss of telomere function. The fact that the main defect detected in mTR-/- embryos is in the closing of the neural tube, suggests that this developmental process is among the most sensitive to telomere loss and chromosomal instability.  (+info)

Generation and characterization of human smooth muscle cell lines derived from atherosclerotic plaque. (8/4834)

The study of atherogenesis in humans has been restricted by the limited availability and brief in vitro life span of plaque smooth muscle cells (SMCs). We describe plaque SMC lines with extended life spans generated by the expression of the human papillomavirus (HPV)-16 E6 and E7 genes, which has been shown to extend the life span of normal adult human aortic SMCs. Resulting cell lines (pdSMC1A and 2) demonstrated at least 10-fold increases in life span; pdSMC1A became immortal. The SMC identity of both pdSMC lines was confirmed by SM22 mRNA expression. pdSMC2 were generally diploid but with various structural and numerical alterations; pdSMC1A demonstrated several chromosomal abnormalities, most commonly -Y, +7, -13, anomalies previously reported in both primary pdSMCs and atherosclerotic tissue. Confluent pdSMC2 appeared grossly similar to HPV-16 E6/E7-expressing normal adult aortic SMCs (AASMCs), exhibiting typical SMC morphology/growth patterns; pdSMC1A displayed irregular cell shape/organization with numerous mitotic figures. Dedifferentiation to a synthetic/proliferative phenotype has been hypothesized as a critical step in atherogenesis, because rat neonatal SMCs and adult intimal SMCs exhibit similar gene expression patterns. To confirm that our pdSMC lines likewise express this apparent plaque phenotype, osteopontin, platelet-derived growth factor B, and elastin mRNA levels were determined in pdSMC1A, pdSMC2, and AASMCs. However, no significant increases in osteopontin or platelet-derived growth factor B expression levels were observed in either pdSMC compared with AASMCs. pdSMC2 alone expressed high levels of elastin mRNA. Lower levels of SM22 mRNA in pdSMC1A suggested greater dedifferentiation and/or additional population doublings in pdSMC1A relative to pdSMC2. Both pdSMC lines (particularly 1A) demonstrated high message levels for matrix Gla protein, previously reported to be highly expressed by human neointimal SMCs in vitro. These results describe 2 novel plaque cell lines exhibiting various features of plaque SMC biology; pdSMC2 may represent an earlier plaque SMC phenotype, whereas pdSMC1A may be representative of cells comprising an advanced atherosclerotic lesion.  (+info)

Using in situ hybridisation, we identified interstitial telomeric sequences in seven chromosomal translocations present in normal and in syndromic subjects. Telomeric sequences were also found at the centromeric ends of a 4p and a 4q caused by centric fission of one chromosome 4. We found that rearrangements leading to interstitial telomeric sequences were of three types: (1) termino-terminal rearrangements with fusion of the telomeres of two chromosomes, of which we report one case; (2) rearrangements in which an acentric fragment of one chromosome fuses to the telomere of another chromosome. We describe four cases of Prader-Willi syndrome with the 15q1-qter transposed to the telomeric repeats of different recipient chromosomes; (3) telomere-centromere rearrangements in which telomeric sequences of one chromosome fuse with the centromere of another chromosome. We describe two examples of these rearrangements in which not only telomeric sequences but also remnants of alphoid sequences were found ...
Figure 1. Telomere-specific FISH in prostate adenocarcinomas. A-D, examples of telomere length and cell-to-cell variability in telomere length in malignant and benign prostate tissue from men in the HPFS who were surgically treated for clinically localized prostate cancer. A, this case has strikingly variable telomere signals among the cancer cells. B, this case has extremely short telomere signals and low variability in telomere length from cancer cell to cancer cell. C, this case has weak telomere signals in the CAS cells. D, this case has strong telomere signals in CAS cells. In all of the images, the DNA is stained with DAPI (blue) and telomere DNA is stained with the Cy3-labeled telomere-specific peptide nucleic acid probe (red). Of note, the centromere DNA, stained with the FITC-labeled centromere-specific peptide nucleic acid probe, has been omitted from the image to emphasize the differences in the telomere lengths. In all panels, the asterisks highlight the cancer cells and the arrows ...
Sergei Mirkin, Tufts University, Medford, speaks on Mechanisms of genome instability mediated by interstitial telomeric sequences. This movie has been recorded by ICGEB Trieste at At... - Lyssna på S. Mirkin - Mechanisms of genome instability mediated by interstitial telomeric sequences av At the Intersection of DNA Replication and Genome Maintenance: from Mechanisms to Therapy direkt i din mobil, surfplatta eller webbläsare - utan app.
Previously, we observed that heterochromatic 4 and Y chromosomes that had experienced breakage in the male germline were frequently transmitted to progeny. Their behavior suggested that they carried functional telomeres. Here we show that efficient healing by de novo telomere addition is not unique to heterochromatic breaks. ...
Telomeres, the physical ends of chromosomes, play an important role in preserving genomic integrity. This protection is supported by telomere binding proteins collectively known as the shelterin complex. The shelterin complex protects chromosome ends by suppressing DNA damage response and acting as a regulator of telomere length maintenance by telomerase, an enzyme that elongates telomeres. Telomere dysfunction manifests in different forms including chromosomal end-to-end fusion, telomere shortening and p53-dependent apoptosis and/or senescence. An important shelterin-associated protein with critical role in telomere protection in human and mouse cells is the catalytic subunit of DNA-protein kinase (DNA-PKcs). DNA-PKcs deficiency in mouse cells results in elevated levels of spontaneous telomeric fusion, a marker of telomere dysfunction, but does not cause telomere length shortening. Similarly, inhibition of DNA-PKcs with chemical inhibitor, IC86621, prevents chromosomal end protection through mechanism
Telomeres are the outermost parts of linear chromosomes. They consist of tandemly repeated non-coding short nucleotide sequences (TTAGGG in all vertebrates), in humans spanning over the last 2 to 15 kilobase pairs of the chromosome. Due to the end-replication problem, telomeres shorten with each cellular division. A critically short telomere will trigger the cell to enter a state of cellular senescence or to apoptose. The rate of telomere shortening can be accelerated by factors such as oxidative stress and inflammation. Taken together, this contributed to making telomere length a candidate biomarker of health and aging. Studies have shown that leukocyte telomere length progressively shortens with age, and that it independent of age is associated with age-related morbidity, lifestyle factors, and mortality. This thesis was aimed at exploring the relationships of leukocyte telomere length with various functional and structural attributes of the brain.. In Paper I, telomere length was shown to be ...
Background: Telomere length dysregulation plays a major role in cancer development and aging. Telomeres are maintained by a group of specialized genes known as shelterin and shelterin-associated proteins. In breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic conversion of the mammary epithelial cells. Interestingly, the regulation of some of the shelterin genes is thought to be controlled epigenetically. Methods and Results: In this study, we set out to measure the effect of increased shelterin gene expression on telomere length in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR) using known telomere length assays. We measured telomere lengths using: Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic levels of 5-aza-CdR affect telomere ...
The SNP rs398652 on 14q21 and several other promising genetic variants were associated in our GWAS with telomere length in leukocytes. We then found that rs398652 was also associated with reduced bladder cancer risk. This SNP is located within the region of 14q that has a high linkage with leukocyte telomere length and is fewer than 450 kb from a microsatellite marker (D14S285) shown to have a very high logarithm (base 10) of odds (LOD) of approximately 3.5 for linkage with telomere length in a previous genetic linkage analysis (27). Furthermore, our mediation analysis to dissect the relationship between rs398652, telomere length, and bladder cancer risk suggests that the association of this SNP with bladder cancer is partially mediated by telomere length.. Telomere shortening and telomerase activation are critical early events of tumorigenesis. Results from a number of epidemiologic studies suggest that shorter telomere length in leukocytes is associated with increased cancer risks for several ...
Human telomeres can be maintained by the enzyme telomerase, which catalyses the addition of telomere repeats, or by the Alternative Lengthening of Telomeres (ALT) mechanism, which is recombination based. Recently, knockout mouse cell lines have indicated that epigenetic modifications associated with telomeric and subtelomeric chromatin, including DNA methylation, Histone 3 Lysine 9 (H31K9) trimethylation and Histone 4 Lysine 20 (H4K20) trimethylation, play an important role in influencing the choice of telomere maintenance mechanism. In this thesis, the levels of these modifications were studied in telomeric chromatin and in the telomere adjacent chromatin of the short arm of the human sex chromosomes (XpYp) in a panel of six human cell lines utilising different telomere maintenance mechanisms. In marked contrast to mouse models, no relationship was found between the level of any of these modifications and telomere maintenance pathway. This may indicate that the role such marks play at telomeres ...
The protective caps on chromosome ends - known as telomeres - consist of DNA and associated proteins that are essential for chromosome integrity. A fundamental part of ensuring proper telomere function is maintaining adequate length of the telomeric DNA tract. Telomeric repeat sequences are synthesized by the telomerase reverse transcriptase, and, as such, telomerase is a central player in the maintenance of steady-state telomere length. Evidence from both yeast and mammals suggests that telomere-associated proteins positively or negatively control access of telomerase to the chromosome terminus. In yeast, positive regulation of telomerase access appears to be achieved through recruitment of the enzyme by the end-binding protein Cdc13p. In contrast, duplex-DNA-binding proteins assembled along the telomeric tract exert a feedback system that negatively modulates telomere length by limiting the action of telomerase. In mammalian cells, and perhaps also in yeast, binding of these proteins probably ...
The CDC13 gene has previously been implicated in the maintenance of telomere integrity in Saccharomyces cerevisiae. With the use of two classes of mutations, here it is shown that CDC13 has two discrete roles at the telomere. The cdc13-2est mutation perturbs a function required in vivo for telomerase regulation but not in vitro for enzyme activity, whereas cdc13-1ts defines a separate essential role at the telomere. In vitro, purified Cdc13p binds to single-strand yeast telomeric DNA. Therefore, Cdc13p is a telomere-binding protein required to protect the telomere and mediate access of telomerase to the chromosomal terminus.. ...
Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular
Replication-based telomere shortening during lifetime is species- and tissue-specific, however, its impact on healthy aging is unclear. In particular, the contribution of telomere truncation to the aging process of the CNS, where replicative senescence alone fails to explain organ aging due to low to absent mitotic activity of intrinsic populations, is undefined. Here, we assessed changes in relative telomere length in non-replicative and replicative neural brain populations and telomerase activity as a function of aging in C57BL/6 mice. Telomeres in neural cells and sub-selected neurons shortened with aging in a cell cycle-dependent and -independent manner, with preponderance in replicative moieties, implying that proliferation accelerates, but is not prerequisite for telomere shortening. Consistent with this telomere erosion, telomerase activity and nuclear TERT protein were not induced with aging. Knockdown of the Rela subunit of NF-κB, which controls both telomerase enzyme and subcellular
Telomeres are the ends of eukaryotic chromosomes, consisting of consecutive short repeats that protect chromosome ends from degradation. Telomeres shorten with each cell division, leading to replicative cell senescence. Deregulation of telomere length homeostasis is associated with the development of various age-related diseases and cancers. A number of experimental techniques exist for telomere length measurement; however, until recently, the absence of tools for extracting telomere lengths...
a) Mammalian telomeres consist of tandem repeats of the TTAGGG sequence that are bound by the shelterin-telosome protein complex. Adjacent to telomeres are the subtelomeric regions, which are also rich in repetitive DNA. (b) In addition to shelterin, mammalian telomeres also contain nucleosomes that show histone modifications characteristic of heterochromatin domains. In addition, subtelomeric DNA is heavily methylated. These chromatin modifications at telomeres and subtelomeres have been shown to negatively regulate telomere length and telomere recombination. TriM, trimethyl. Image and legend from Telomere length, stem cells and aging.. You can also have a look at the diagrams related to telomere extension in my 2011 blog entry The epigenetic regulation of telomeres.. Shortened telomeres is only one of a number of factors that can contribute to cellular senescence, and may often be a downstream effect of such factors.. Apostles of telomere-extending would lead us to believe that cell ...
Newborn telomere length sets telomere length for later life. At birth, telomere length is highly variable among newborns and the environmental factors during in utero life for this observation remain largely unidentified. Obesity during pregnancy might reflect an adverse nutritional status affecting pregnancy and offspring outcomes, but the association of maternal pre-pregnancy body mass index (BMI) with newborn telomere length, as a mechanism of maternal obesity, on the next generation has not been addressed. Average relative telomere lengths were measured in cord blood (n = 743) and placental tissue (n = 702) samples using a quantitative real-time PCR method from newborns from the ENVIRONAGE birth cohort in Belgium. By using univariate and multivariable adjusted linear regression models we addressed the associations between pre-pregnancy BMI and cord blood and placental telomere lengths. Maternal age was 29.1 years (range, 17-44) and mean (SD) pre-pregnancy BMI was 24.1 (4.1) kg/m2. Decline in newborn
Almost 12 years ago, an evolutionary theory based on intergenerational telomere erosion was introduced [8] and was widely covered by the press [11, 12]. In 2011, based on published data on human telomere length inheritance, I refined my theoretical framework and located the source of human intergenerational telomere erosion in the female germline [6, 7, 10]. According to this model, telomeres in the testes of elderly males are longer than those in young males because the seniors are members of a previous generation (=birth-cohort effect) and therefore skipped, on average, one female-based intergenerational telomere loss. In 2014, I further developed the model of telomere-driven macroevolution and presented a complete biological framework for the old European model of saltatory evolution of nonadaptive characters [6].. In agreement with this theoretical model, a high-profile study, published in the August issue of Aging Cell in 2015, finally confirmed the long-awaited birth-cohort effect on ...
Telomere length analysis of donor-derived bone marrow cells (Fig. 3) and HSCs (Fig. 4) shows substantial telomere shortening during serial HSC transplantation. The difference in mean TRF length (ΔTRF) of bone marrow cells after one round of HSC transplantation is ∼1.5 kb (Fig. 3 B). This agrees reasonably well with the predicted reduction in telomere size assuming that ΔTRF is mainly due to the minimum number of extra population doublings (∼12-13) required for expansion of the fraction of the transplanted HSC population which engraft to the size of the HSC pool in adult mice (∼3-5 × 104 cells; references 3, 4), and that the rate of telomere shortening during division of the transplanted HSCs is 50-100 bp per population doubling, as observed for other mouse cells 14,39,40. However, the extent of telomere shortening during the second round of HSC transplantation (ΔTRF ≈ 5.5 kb) is considerably greater than ΔTRF during the first round of transplantation (Fig. 3). One possible ...
The results described in this study provided evidences that SYUIQ5, a Gquadruplex ligand, potently inhibited the proliferation and induced telomere DNA damage and autophagy in CNE2 and HeLa cancer cells in vitro. TRF2 delocalized from telomeres after SYUIQ5 treatment and was further degraded by proteasomes. In addition, overexpression of TRF2 prevented SYUIQ5-mediated cell death. ATM was also activated and involved in SYUIQ-5-induced telomere DNA damage response and autophagy. Furthermore, ATG5 knockdown attenuated the cytotoxicity of SYUIQ-5 in CNE2 and HeLa cells.. Telomeres are capable of forming guanine quadruplex (G4) structures on the G-rich strand, and the ligands that interact with G-quadruplex are recognized as promising anticancer agents by interfering with telomere conformation and telomere elongation. These compounds were first evaluated as telomerase inhibitors and induced telomere shortening and senescence. Recently, it was observed that G-quadruplex ligands induced a short-term ...
Debido al estado altamente heterocromatinizado del telómero se pensaba que el final de los cromosomas no era transcrito. Sin embargo, hace una década se demostró que los telómeros se transcriben en una familia de lncRNAs denominados Telomeric repeat-containing RNA o TERRA. En los últimos años, un gran número de funciones diferentes han sido asociadas a estos transcritos. Sin embargo, la falta de modelos genéticos KO para TERRA ha impedido confirmar estas funciones en sistemas celulares. La falta de modelos se debe mayoritariamente a que su origen subtelomérico no está claro. En humanos, los estudios más recientes han propuesto que TERRA se podría transcribir de 18 loci diferentes, dificultando en gran medida la generación de células KO para TERRA. Uno de los principales objetivos de mi tesis, ha sido identificar los posibles loci de TERRA humanos, con el objetivo de generar células humanas KO para TERRA. Primero evaluamos los 18 loci previamente descritos, encontrando que el 80% ...
In human cells, homologous recombination (HR) provides an accurate mechanism for the repair of DNA double-strand breaks caused by replication fork breakdown or DNA damaging agents. HR also plays a role in the maintenance of eukaryotic telomeres; cells defective in the recombinational repair proteins RAD51D or RAD54 exhibit telomere shortening and end-to-end chromosome fusions. Here we discuss the way in which HR contributes to telomere protection and elongation in mammalian cells. Understanding the mechanisms by which HR promotes telomere maintenance has important implications for genomic stability and tumorigenesis.
Telomeres are complex nucleoprotein structures that protect the extremities of linear chromosomes. Telomere replication is a major challenge because many obstacles to the progression of the replication fork are concentrated at the ends of the chromosomes. This is known as the telomere replication problem. In this article, different and new aspects of telomere replication, that can threaten the integrity of telomeres, will be reviewed. In particular, we will focus on the functions of shelterin and the replisome for the preservation of telomere integrity
4. The Curious Case of Skeletal Muscle Telomere Biology in Humans Skeletal muscle has unique telomere biology when compared to other tissues. Skeletal muscle consists of a syncytium of multinucleated muscle fibers that are postmitotic; thus, telomere length should remain stable in this population of nuclei, with the rare exception of DNA damaging stimuli [89]. In addition to myonuclei, single-nucleated populations of cells, of which the best described are satellite cells, also populate skeletal muscle [90]. Satellite cells are muscle precursor cells (i.e., adult stem cells) that are quiescent unless induced to divide by external stressors, such as contraction-induced or injury-induced muscle damage [90]. When induced to divide, satellite cells divide asymmetrically, with one daughter cell incorporating into the damaged muscle fiber and the other daughter cell returning to replenish the satellite cell pool [90]. Skeletal muscle telomere dogma states that when a muscle precursor cell is induced to ...
It is not the length of telomeres per se that protects against loss of chromosome end function, but the ability to maintain sufficient length to form a functional telomere cap. Although equilibrium telomere lengths vary dramatically between yeast, mice and humans, they share a dosage-sensitive balance between telomere loss and replenishment. In heterozygous mTert mice that have been bred for many generations, we propose that initial telomere attrition followed by eventual recovery reflects such a length-dependent equilibrium. In S. cerevisiae and humans, long telomeres inhibit telomerase access owing to cis-inhibition by telomere-bound factors such as Rif1/Rif2 and TRF1/TRF2, respectively (Smogorzewska and de Lange, 2004; Hug and Lingner, 2006). Once telomeres become short, the dosage of telomere-bound factors is reduced, leading to loss of cis-inhibition and a switch to a telomerase-extendible state (Smogorzewska and de Lange, 2004; Hug and Lingner, 2006). Upon telomere shortening, murine cells ...
We measured the effects of long-term NRTI and NNRTI exposure on telomere length maintenance using the HT29 human colorectal adenocarcinoma cell model (Table 2). HT29 has robust telomerase activities, as measured by the PCR-based telomerase activity assay [31]. HT29 cells were treated with a minimum of two concentrations of NRTIs or NNRTIs. Cell proliferation and growth rate was monitored continuously. Long-term treatment of HT29 cells with AZT is known to cause telomere length attrition [9,10,11,13]. Using the terminal restriction fragment (TRF) assay, we confirmed substantial inhibitory effects of AZT on telomere length maintenance in HT29 cells (Figure 6A and 6B). Mean telomere length was determined as a weighted average with reference to DNA standards. Figure 7. Continuous treatment of HT29 cells with the adenosine analogs TDF and ddI causes observable telomere shortening. A. TRF blots of untreated (left), TDF-treated (right) HT29 cells. PDL at which TRF was analyzed is shown above each lane. ...
Telomeres are ribonucleoprotein structures at the end of chromosomes composed of telomeric DNA, specific-binding proteins and noncoding RNA (TERRA). Despite their importance in preventing chromosome instability, little is known about the crosstalk between these three elements during the formation of the germ line. Here, we provide evidence that both TERRA and the telomerase enzymatic subunit (TERT) are components of telomeres in mammalian germ cells. We found that TERRA co-localizes with telomeres during mammalian meiosis and that its expression progressively increases during spermatogenesis, until the beginning of spermiogenesis. While both TERRA levels and distribution would be regulated in a gender-specific manner, telomere-TERT co-localization appears to be regulated based on species-specific characteristics of the telomeric structure. Moreover, we found that TERT localization at telomeres is maintained all through spermatogenesis as a structural component without affecting telomere ...
Single-stranded DNA-dependent ATP-dependent helicase. Involved in non-homologous end joining (NHEJ) DNA double strand break repair. DNA-binding is sequence-independent but has a high affinity to nicks in double-stranded DNA and to the ends of duplex DNA. Binds to naturally occurring chromosomal ends, and therefore provides chromosomal end protection. Appears to have a role in recruitment of telomerase and CDC13 to the telomere and the subsequent telomere elongation. Required also for telomere recombination to repair telomeric ends in the absence of telomerase. KU70, of the KU70/KU80 heterodimer, binds to the stem loop of TLC1, the RNA component of telomerase. Involved in telomere maintenance. Interacts with telomeric repeats and subtelomeric sequences thereby controlling telomere length and protecting against subtelomeric rearrangement. Maintains telomeric chromatin, which is involved in silencing the expression of genes located at the telomere. Required for mating-type switching.
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
One of the factors limiting indefinite proliferation of somatic cells is telomere length [1], [2]. Indeed, the inability to fully replicate both strands of a linear DNA molecule is expected to lead to gradual shortening of telomeres in cells that do not express telomerase. Telomere shortening may be even more severe, if the replication machinery fails to reach the telomeric end. Indeed, the highly repetitive primary structure of telomeres [3], the presence of G‐quadruplexes [4], DNA-RNA hybrids [5], [6], and T‐loops [7], as well as the extensive telomeric heterochromatinization [8], challenge the process of terminal DNA replication and make telomeres prone to fork collapse, similar to common fragile sites [9], [10]. Fork collapse within a telomere is unlikely to be resolved by incoming forks or dormant forks, since human telomeres are thought to be devoid of replication origins. Instead, telomere replication is normally dependent on a single origin, located at the subtelomeric regions [11]. ...
Mutations accumulate as a result of DNA damage and imperfect DNA repair machinery. In higher eukaryotes the accumulation and spread of mutations is limited in two primary ways: through p53-mediated programmed cell death and cellular senescence mediated by telomeres. Telomeres shorten at every cell division and cell stops dividing once the shortest telomere reaches a critical length. It has been shown that the rate of telomere attrition is accelerated when cells are exposed to DNA damaging agents. However the implications of this mechanism are not fully understood. With the help of in silico model we investigate the effect of genotoxic stress on telomere attrition and apoptosis in a population of non-identical replicating cells. When comparing the populations of cells with constant vs. stress-induced rate of telomere shortening we find that stress induced telomere shortening (SITS) increases longevity while reducing mutation rate. Interestingly, however, the effect takes place only when genotoxic
TY - JOUR. T1 - Telomere length dynamics and chromosomal instability for predicting individual radiosensitivity and risk via machine learning. AU - Luxton, Jared J.. AU - McKenna, Miles J.. AU - Lewis, Aidan M.. AU - Taylor, Lynn E.. AU - Jhavar, Sameer G.. AU - Swanson, Gregory P.. AU - Bailey, Susan M.. N1 - Funding Information: Funding: This research was funded by the Colorado Office of Economic Development and International Trade (OEDIT) Advanced Industry (AI) Bioscience Proof of Concept (POC) award program, Colorado State University (CSU) Ventures. Graduate student fellowships awarded by CSUs Program of Research and Scholarly Excellence (PRSE), and the Cancer Biology and Comparative Oncology (CB&CO) PRSE to support quantitative Cell and Molecular Biology (qCMB) studies, are also gratefully acknowledged. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.. PY - 2021/3. Y1 - 2021/3. N2 - The ability to predict a cancer patients response to radiotherapy and risk ...
The TeloYears test is not intended for screening, diagnosing, treating or preventing diseases or medical conditions. The TeloYears genetic test may indicate the possibility of identifying a rare telomere syndrome associated with extremely shorter or longer average telomere length (ATL). In these rare cases, further testing and consultation with a doctor to rule in or rule out a telomere syndrome is recommended. The test is available for individuals between the ages of 20 to 80 within the United States, except for the states of Maryland and New York. The information provided by the TeloYears test should not be used to replace medically appropriate screening tests recommended based upon actual age or other risk factors, nor should the information be used to make decisions about diagnosis or treatment of diseases or medical conditions. The Telomere Diagnostics lab is regulated under the Clinical Laboratory improvement Amendments of 1988 (CLIA) as qualified to perform high complexity clinical ...
Telomeres are specific nucleoprotein structures at the ends of eukaryotic chromosomes. Telomeres and telomere-associated proteins maintain genome stability by protecting the ends of chromosomes from fusion and degradation. In normal somatic cells, the length of the telomeres gradually becomes shortened with cell division. In tumor cells, the shortening of telomeres length is accelerated under the increased proliferation pressure. However, it will be maintained at an extremely short length as the result of activation of telomerase. Significantly shortened telomeres, activation of telomerase, and altered expression of telomere-associated proteins are common features of various hematologic malignancies and are related with progression or chemotherapy resistance in these diseases. In patients who have received hematopoietic stem cell transplantation (HSCT), the telomere length and the telomerase activity of the engrafted donor cells have a significant influence on HSCT outcomes. Transplantation-related
Understanding the molecular processes that drive cellular replicative senescence is critical to understanding human longevity. Much attention has focused on telomere length as a determinant of replicative capacity (1). Telomeres are nucleoprotein structures composed of species-specific tandemly repeated, G-rich DNA sequences that cap and protect chromosome ends from nucleolytic attack and degradation (2). Telomeres also conceal linear chromosome ends from inappropriate attempts at double-strand break (DSB) repair that might otherwise join chromosomes end-to-end. The preservation of natural chromosome ends and the rejoining of broken DNA ends, both of which are essential for preserving genomic integrity, rely on a common subset of proteins (3), and both decline with advancing age (4, 5).. The G-rich nature of telomeric DNA renders it susceptible to G-quadruplex formation, oxidative damage, and alkylation by electrophiles (6). Telomeres are also unique in their chromatin composition, being bound ...
The Patient Telomere Score is calculated based on the patients average telomere length in peripheral whole blood cells. This average is then compared to telomere lengths from a population sample in the same age range as the patient to determine the patients percentile score. What do the results mean to the patient and the doctor? Cellular attrition by analyzing the rate at which changes in average Telomere length occur over time. Cells are being lost and replaced. (Cellular attrition) What are the nutritional implications on telomere length and repair? An inflammatory diet, or one that increases oxidative stress, will shorten telomeres faster. This includes refined carbohydrates, fast foods, processed foods, sodas, artificial sweeteners, trans fats and saturated fats. A diet with a large amount and variety of antioxidants that improves oxidative defense and reduces oxidative stress will slow telomere shortening. Consumption of 10 servings of fresh and relatively uncooked fruits and vegetables, ...
Why is this important In embryonic cells (and some stem cells), an enzyme called telomerase rebuilds the telomere so that the cells can keep dividing. Over time, this telomerase dwindles and eventually the telomere shortens and the cell becomes inactive. In cancer cells, the telomerase enzyme keeps rebuilding telomeres long past the cells normal lifetime. The cells become immortal, endlessly dividing, resulting in a tumor. Researchers estimate that telomere maintenance activity occurs in about 90% of human cancers. But the mechanism by which this maintenance takes place is not well understood. The researchers discovered that the RNA in the telomere is regulated by a protein in the telomerase enzyme. Their discovery may thus uncover key elements of telomere function ...
TY - JOUR. T1 - Telomere length in peripheral blood leukocytes and risk of renal cell carcinoma. AU - Park, Jong Y.. AU - Luu, Hung N.. AU - Park, Hyun Y.. AU - Lin, Hui Yi. AU - Radlein, Selina. AU - Di Pietro, Giuliano. AU - Yeo, Chang Dong. AU - Kim, Seung Joon. AU - Kang, Nahyeon. AU - Antwi, Samuel. AU - Sexton, Wade J.. AU - Spiess, Philippe E.. AU - Dickinson, Shohreh. AU - Parker, Alexander. PY - 2019/1/1. Y1 - 2019/1/1. N2 - Background: Telomeres are essential for chromosomal stability and may play a key role in carcinogenesis. Telomere length is suggested as a tentative biomarker of risk for renal cell carcinoma (RCC). However, results of previous association studies between telomere length and risk for RCC are inconsistent. Methods: We evaluated RCC risk in relation to peripheral blood leukocyte telomere length using a hospital-based case-control study of 169 RCC cases and 189 controls. Cases were histologically-confirmed RCC patients who were treated at the Moffitt Cancer Center ...
An SGA approach to discover cdc13-1ts supressors. Telomeres, the DNA-protein complexes at the end of eukaryotic chromosomes, are essential for chromosomal stability. In yeast, the telomeric single-strand binding protein Cdc13p has multiple important roles related to telomere maintenance: (1) telomericcapping--protection of telomeres by forming complexes with yKu70/80 and with Stn1p/Ten1p; (2) positive regulation of telomere replication via interaction with Est1p, which is a part of telomerase; (3) negative regulation of telomerase by the recruitment of telomere elongation suppressors Stn1p and Ten1p. In an attempt to identify genes that are involved in the deleterious outcome of an absence of Cdc13p, we screened the yeast gene knock-out library for genes that could suppress the growth defect of cdc13-1 cells at 33ê C. For this purpose, we performed an SGA array experiment. We scored for the ability of double mutant haploids to grow at 33ê C. Eventually, we hoped to find the elusive genes ...
Laure Crabbe, Ramiro E. Verdun, Candy I. Haggblom, and Jan Karlseder http://sageke.sciencemag.org/cgi/content/abstract/2004/50/or22 Abstract: Science 306, 1951-1953 (2004).. Cells from Werner syndrome patients are characterized by slow growth rates, premature senescence, accelerated telomere shortening rates, and genome instability. The syndrome is caused by the loss of the RecQ helicase WRN, but the underlying molecular mechanism is unclear. Here we report that cells lacking WRN exhibit deletion of telomeres from single sister chromatids. Only telomeres replicated by lagging strand synthesis were affected, and prevention of loss of individual telomeres was dependent on the helicase activity of WRN. Telomere loss could be counteracted by telomerase activity. We propose that WRN is necessary for efficient replication of G-rich telomeric DNA, preventing telomere dysfunction and consequent genomic instability.. [Abstract/Full Text]. ...
We have isolated STN1, an essential Saccharomyces cerevisiae gene, as a suppressor of the cdc13-1 mutation. A synthetic lethal interaction between a temperature-sensitive mutant allele of STN1, stn1-13, and cdc13-1 was observed. Stn1 and Cdc13 proteins displayed a physical interaction by two-hybrid analysis. As shown previously for cdc13-1, stn1-13 cells at the restrictive temperature accumulate single-stranded DNA in subtelomeric regions of the chromosomes, but to a lesser extent than cdc13-1 cells. In addition, both Cdc13 and Stn1 were found to be involved in the regulation of telomere length, mutations in STN1 or CDC13 conferring an increase in telomere size. Loss of Stn1 function activated the RAD9 and MEC3 G2/M checkpoints, therefore confirming that DNA damage is generated. We propose that Stn1 functions in telomere metabolism during late S phase in cooperation with Cdc13 ...
Telomeres, which are found at the end of eukaryotic linear chromosomes, are essential for chromosome maintenance and genomic stability (1). Mammalian telomeres are composed of repetitive d-(TTAGGG) sequences and telomere-specific shelterin complex proteins, which protect the chromosome ends from being recognized as DNA damage and preventing end-to-end chromosomal fusions (2). The shelterin proteins (TRF1, TRF2, POT1, TIN2, TPP1, and RAP1) form a protective complex that is present at telomeres throughout the cell cycle (3). Because of the end-replication problem, oxidative damage and other replication-associated end-processing events, telomeres progressively shorten with each round of DNA replication in normal somatic cells (4). The ribonucleoprotein enzyme complex telomerase counteracts telomere shortening by adding hexameric telomeric DNA (TTAGGG) repeats to the end of linear chromosomes in cancer cells but only partially counteracts progressive telomere shortening in some normal human ...
Figure 3. Mutations in STN1 result in abnormal telomere phenotypes. (A) DNA samples, prepared from PBLs of patient P1, her heterozygous father (F1), and a noncarrier sibling (S1) and patient P2, his heterozygous mother (M2), and two independent control samples (C), were analyzed by in-gel hybridization. Duplicated lanes were electrophoresed in the same gel, and then separated and hybridized to a G-rich or C-rich telomeric probe, as indicated above the panels. After native hybridization to detect single-stranded telomeric DNA (top), the gels were denatured and rehybridized with the same probes to detect the overall duplex telomeric DNA (bottom). Treatment with exonuclease I is indicated above the lanes. (B) Graphic illustration of the mean telomere length for the patients and their family members, calculated based on the following number of independent measurements of four in-gels and two Southern analyses: P1:6, M1:3, F1:3, S1:3, P2:9, M2:3, F2:1, C1:2, and C2:3. (C) Graphic illustration of the ...
Osteoarthritis (OA) and osteoporosis (OP) are associated skeletal pathologies and have as a distinct feature the abnormal reconstruction of the subchondral bone. OA and OP have been characterized as age‑related diseases and have been associated with telomere shortening and altered telomerase activity (TA). This review discusses the role of telomeres and telomerase in OA and OP pathologies and focuses on the usability of telomere length (TL) and the rate of telomere shortening as potential disease biomarkers. A number of studies have demonstrated that telomere shortening may contribute to OA and OP as an epigenetic factor. Therefore, it has been claimed that the measurement of TL of chondrocytes and/or peripheral blood cells may be an appropriate marker for the evaluation of the progression of these diseases. However, there is a need to be perform further studies with larger cohorts, with the aim of obtaining objective results and a better understanding of the association between TL, ...
POT1 is one of the six core components of the human telomeric protein complex (reviewed in de Lange, 2005). This complex is composed of TRF1, TRF2, TIN2, TPP1 (previously known as PIP1, PTOP, or TINT1), Rap1, and POT1, which are thought to fulfill the two main functions of telomeres: the recruitment and regulation of telomerase, and the protection of chromosome ends. Defects in telomere protection activate the DNA damage response, leading to a DNA damage signal and inappropriate DNA repair reactions at chromosome ends. The cell cycle arrest resulting from telomere dysfunction is thought to be responsible for the finite lifespan of human cells lacking telomerase.. The current challenge is to understand how the telomeric complex protects chromosome ends from being recognized as sites of DNA damage. One approach is to define which repair and signaling pathways are repressed at natural chromosome ends by studying the events at dysfunctional telomeres. This approach has shown that chromosome ends are ...
Acts both as a regulator of telomere function and as a transcription regulator. Involved in the regulation of telomere length and protection as a component of the shelterin complex (telosome). In contrast to other components of the shelterin complex, it is dispensible for telomere capping and does not participate in the protection of telomeres against non-homologous end-joining (NHEJ)-mediated repair. Instead, it is required to negatively regulate telomere recombination and is essential for repressing homology-directed repair (HDR), which can affect telomere length. Does not bind DNA directly: recruited to telomeric double-stranded 5-TTAGGG-3 repeats via its interaction with TERF2. Independently of its function in telomeres, also acts as a transcription regulator: recruited to extratelomeric 5-TTAGGG-3 sites via its association with TERF2 or other factors, and regulates gene expression. When cytoplasmic, associates with the I-kappa-B-kinase (IKK) complex and acts as a regulator of the NF-kappa-B
Telomere attrition has been associated with age-related diseases, although causality is unclear and controversial; low-grade systemic inflammation (inflammaging) has also been implicated in age-related pathogenesis. Unpicking the relationship between aging, telomere length (TL), and inflammaging is hence essential to the understanding of aging and management of age-related diseases. This longitudinal study explored whether telomere attrition is a cause or consequence of aging and whether inflammaging explains some of the associations between TL and one marker of aging, grip strength. We studied 253 Hertfordshire Ageing Study participants at baseline and 10-year follow-up (mean age at baseline 67.1 years). Participants completed a health questionnaire and had blood samples collected for immune-endocrine and telomere analysis at both time points. Physical aging was characterized at follow-up using grip strength. Faster telomere attrition was associated with lower grip strength at follow-up (β = 0.98, p =
Depletion of hematopoietic stem cell reserves, expressed as the shortening of leukocyte telomere length (LTL), sets a limit on longevity and increases the risk...
Objective:: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods:: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results:: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of ...
TELOMERES are nucleoprotein complexes at the termini of linear eukaryotic chromosomes that perform a critical role in maintaining genome stability. At the DNA level, telomeres typically comprise long double-stranded tracts of a repetitive GT/CA-rich sequence, terminating in a short single-stranded 3′ overhang that corresponds to the strand bearing the G-rich repeats. A large number of proteins associate with the telomere repeats to form a structure that allows telomeres to act as caps that protect chromosome ends from degradation and illegitimate end-to-end fusions. Chromosomes are considered capped if they preserve the physical integrity of the telomere while allowing cell division to proceed (Blackburn 2000). Proteins that bind to the duplex portion of telomeres, such as TRF1 and TRF2 in mammalian cells and Rap1p in Saccharomyces cerevisiae, as well as proteins that bind the single-strand overhang, such as POT1 in mammalian cells and Cdc13p in S. cerevisiae, are essential for proper ...
CONTEXT: Both leukocyte telomere length and IGF-I are associated with the aging process. A previous in vitro study suggested that IGF-I may modulate telomerase activity in white blood cells, but little is known whether these two systems interact in vivo. PATIENTS AND METHODS: Leukocyte telomere length was determined using a quantitative PCR assay in 2744 elderly men (mean age 75.5 yr, range 69-81 yr) included in the population-based Osteoporotic Fractures in Men-Sweden study. Serum IGF-I concentration was measured using RIA. RESULTS: Subjects with a leukocyte telomere length in the lowest tertile group had lower serum IGF-I concentration than subjects in the two tertile groups with longer telomere lengths (P = 0.005). Logistic regression analyses showed that a higher serum IGF-I concentration was associated with a significantly reduced risk of having a leukocyte telomere length in the lowest tertile group and also after adjustment for multiple covariates (P , 0.01). Multivariate linear ...
Objectives: Telomere erosion, a feature of biological ageing, is implicated in a wide range of diseases. Its impact on autoimmune diseases remains unclear although autoantibodies against many telomere nucleoprotein components are prevalent in these diseases. We aimed to assess if telomere biology was abnormal in a cohort of patients with limited cutaneous systemic sclerosis (lcSSc).. Methods: Telomere lengths in peripheral blood leucocytes (PBL) were determined using Southern blotting methods in a cohort of lcSSc subjects (n = 43; age range 37-80 years) and a control population (n = 107; age range 21-65 years).. Results: Telomere lengths in lcSSc subjects were longer than controls (p,0.001), did not show age-related telomere erosion and differed significantly from age-matched controls only after 50 years of age (p,0.001).. Conclusions: This is the first report of maintenance of telomere lengths in an autoimmune disease state. These data indicate aberrant telomere biology and irregular biological ...
Abstract Bachground The premature ovarian failure (POF) is a reason of infertility that affects about 1-4% of women before age 40. The importance of telomeres length in different diseases has been explored before. This study examines the association between the relative telomere length and idiopathic POF in a group of Iranian women. Methods The blood genomic DNA was extracted from 40 idiopathic POF patients (case group) and 40 fertile women (control group). The relative telomere length (RTL) was evaluated by quantitative Real-Time PCR using specific telomeric primers. RTL was calculated as T (telomere)/S (single copy gene) ratio and compared between infertile and fertile groups. Results A strong association was considered between telomere size and idiopathic premature ovarian failure. In patients the relative telomere length showed to be significantly longer than those of control group (P , .05, 95% CI). Conclusion Our findings demonstrate a possible relationship between telomere lengthening ...
Consumption of sugar-sweetened beverages (SSBs) is linked to increased risks of metabolic disease, but the biological mechanisms underlying this association are still under investigation. Leukocyte telomere length maintenance underlies healthy cellular aging, and may provide a link between SSB consumption and risk of disease. Given the known effects of SSBs on oxidative stress and insulin resistance, we examined the associations between sugar-sweetened beverage, diet soda, and fruit juice consumption, and leukocyte telomere length in 5,309 healthy adults with no prior history of diabetes or cardiovascular disease, using data from the 1999-2002 National Health and Nutrition Surveys (NHANES). We hypothesized that beverages with high sugar content would be most detrimental to cellular aging. Leukocyte telomere length was assayed from DNA specimens collected from adult NHANES participants. Diet was assessed using 24-hour dietary recalls. Because 24-hour dietary recalls may not accurately reflect ...
TY - JOUR. T1 - Crystal structure of the two-RRM domain of hnRNP A1 (UP1) complexed with single-stranded telomeric DNA. AU - Ding, Jianzhong. AU - Hayashi, Mariko K.. AU - Zhang, Ying. AU - Manche, Lisa. AU - Krainer, Adrian R.. AU - Xu, Rui Ming. PY - 1999/5/1. Y1 - 1999/5/1. N2 - Human hnRNP A1 is a versatile single-stranded nucleic acid-binding protein that functions in various aspects of mRNA maturation and in telomere length regulation. The crystal structure of UP1, the amino-terminal domain of human hnRNP A1 containing two RNA-recognition motifs (RRMs), bound to a 12- nucleotide single-stranded telomeric DNA has been determined at 2.1 Å resolution. The structure of the complex reveals the basis for sequence- specific recognition of the single-stranded overhangs of human telomeres by hnRNP A1. It also provides insights into the basis for high-affinity binding of hnRNP A1 to certain RNA sequences, and for nucleic acid binding and functional synergy between the RRMs. In the crystal ...
Telomere dysfunction-induced loss of genome integrity and its associated DNA damage signaling and checkpoint responses are well-established drivers that cause tissue degeneration during ageing. Cancer, with incidence rates greatly increasing with age, is characterized by short telomere lengths and high telomerase activity. To study the roles of telomere dysfunction and telomerase reactivation in ageing and cancer, the protocol shows how to generate two murine inducible telomerase knock-in alleles 4-Hydroxytamoxifen (4-OHT)-inducible TERT-Estrogen Receptor (mTERT-ER) and Lox-Stopper-Lox TERT (LSL-mTERT). The protocol describes the procedures to induce telomere dysfunction and reactivate telomerase activity in mTERT-ER and LSL-mTERT mice in vivo. The representative data show that reactivation of telomerase activity can ameliorate the tissue degenerative phenotypes induced by telomere dysfunction. In order to determine the impact of telomerase reactivation on tumorigenesis, we generated prostate ...
TY - JOUR. T1 - Stabilization of telomere length and karyotypic stability are directly correlated with the level of hTERT gene expression in primary fibroblasts. AU - Cui, Wei. AU - Aslam, Samena. AU - Fletcher, Judy. AU - Wylie, Diana. AU - Clinton, Michael. AU - Clark, A John. PY - 2002. Y1 - 2002. N2 - Telomere shortening and lack of telomerase activity have been implicated in cellular senescence in human fibroblasts. Expression of the human telomerase (hTERT) gene in sheep fibroblasts reconstitutes telomerase activity and extends their lifespan. However, telomere length is not maintained in all cell lines, even though in vitro telomerase activity is restored in all of them. Cell lines expressing higher levels of hTERT mRNA do not exhibit telomere erosion or genomic instability. By contrast, fibroblasts expressing lower levels of hTERT do exhibit telomere shortening, although the telomeres eventually stabilize at a shorter length. The shorter telomere lengths and the extent of karyotypic ...
Schizophrenia is a complex neurodevelopmental disorder characterized by mental dysfunction in multiple domains of the brain (46). Previous studies have shown lower telomere length in patients with schizophrenia and paranoid schizophrenia compared to control groups (47,48). Patients suffering from paranoid schizophrenia, who were under anti-psychotics medication had slightly decreased leukocyte telomere length. In addition, telomere length analysis of paranoid schizophrenic patients revealed that response to treatment influences telomere length with poor responders having the shorter telomeres (49). By contrast, other authors have shown that the poor responders had the shortest terminal restriction fragments (TRFs) which was inversely associated with age. Furthermore, Fernandez-Egea et al (19), who included both men and women, showed that the whole psychosis group had decreased telomere content compared to the control group and that both men and women had the same telomere content. However, when ...
Telomeres maintain genomic integrity in normal cells, and their progressive shortening during successive cell divisions induces chromosomal instability. In the large majority of cancer cells, telomere length is maintained by telomerase. Thus, telomere length and telomerase activity are crucial for cancer initiation and the survival of tumors. Several pathways that regulate telomere length have been identified, and genome-scale studies have helped in mapping genes that are involved in telomere length control. Additionally, genomic screening for recurrent human telomerase gene hTERT promoter mutations and mutations in genes involved in the alternative lengthening of telomeres pathway, such as ATRX and DAXX, has elucidated how these genomic changes contribute to the activation of telomere maintenance mechanisms in cancer cells. Attempts have also been made to develop telomere length- and telomerase-based diagnostic tools and anticancer therapeutics. Recent efforts have revealed key aspects of telomerase
Telomeres are the caps that form ends of human chromosomes to protect the DNA strands from becoming damaged. The word telomere comes from the Greek words telos (end) and meros (part). Throughout our lives, our cells need to replenish by copying themselves (also known as cell division). The downside of this process is that the telomeres shorten each time a cell copies itself. Eventually, when the telomeres get so short that cant do their job, cells will age and stop functioning properly. This essentially means that telomeres are our cells biological clocks - their length represents our biological age as opposed to our chronological age.. Although the shortening of telomeres can suppress tumors, there is growing evidence that telomere shortening also restricts stem cell function, organ maintenance, and regeneration. During aging and disease, telomere shortening can also increase risk of cancer. ...
Electrochemical behavior of the anticancer doxorubicin hydrochloride( DOX) and the interaction of DOX with human telomere DNA were investigated by cyclic voltammetry in aqueous medium using p H 6. 0 PBS buffer. The results showed that a pair of reversible oxidation- reduction peaks were observed at- 0. 585 V and- 0. 638 V in p H 6. 0 PBS buffer. There existed excellent linearities between oxidation peak current and concentration of DOX in the ranges of 0. 03- 0. 8 μmol/L and0. 8- 10 μmol/L by linear sweep voltammetric method. Detection limit( S/N = 3) was 0. 01 μmol /L. The relative standard deviations of the oxidation peak current obtained from 11 determinations of the same solutions containing 0. 5 μmol/L DOX were 3. 5%. The oxidation peak current of DOX gradually decreased with the adding of various concentrations of human telomere DNA,due to interaction of DOX with human telomere DNA. The binding ratio was calculated to be 1 ∶ 1 and the binding equilibrium constant was 1. 11 × 103 L/mol.
In this study, we identify decreased dyskerin protein levels as a novel mechanism of disease in X-linked DC. In affected individuals, despite the presence of an intact coding sequence, decreased dyskerin levels were associated with reduced hTR stability and telomere shortening. Knockdown of dyskerin levels has been previously shown to decrease hTR levels in cancer cell lines,39 40 although its consequences on telomere length have not been examined. Our data indicate that intact dyskerin levels, and not only protein sequence, are essential for in vivo telomere maintenance, and this defect is sufficient to cause premature mortality due to telomere mediated disease. In half of X-linked DC families, the mechanism of disease is not known. Our data, if replicated in larger cohorts, would suggest that quantitation of dyskerin protein levels can complement sequencing of the DKC1 gene, and decreased levels of dyskerin, measured by sensitive methods, can identify male carrier status in a subset of ...
Telomerase, the ribonucleoprotein complex involved in telomere maintenance, is composed of two main components: hTERT and hTERC. hTERT seems to be the rate-limiting factor for telomerase activity, although hTERC expression was also shown to correlate to a certain extent with telomerase reactivation. To determine whether the absence of hTERC expression could be the consequence of DNA methylation, we quantified hTERC RNA in 60 human samples (19 telomerase-negative normal tissues, nine telomerase-positive and 22 telomerase-negative tumor tissues, eight telomerase-positive and two telomerase-negative cell lines) using a quantitative dot blot on RT-PCR products. Most of the normal tissues did not express hTERC whereas, in telomerase-positive cell lines and in telomerase-positive tumor tissues, a strong up-regulation was observed, suggesting that hTERC transcription is up-regulated during tumorigenesis. The two telomerase-negative cell lines did not express hTERC. In a series of 22 telomerase-negative ...
in Anticancer Research (2008), 28(5c), 3257-3258. Telomeres consist of protein complexes and repeated TTAGGG double strand DNA sequences ended by a 3 single strand DNA of the same sequence. Progressive telomere shortening is observed in vitro upon ... [more ▼]. Telomeres consist of protein complexes and repeated TTAGGG double strand DNA sequences ended by a 3 single strand DNA of the same sequence. Progressive telomere shortening is observed in vitro upon cell divisions and with ageing in vivo. At a critical telomere length, shortened telomeres trigger a permanent growth arrest known as replicative senescence. Telomerase is an RNA-dependent DNA polymerase that extends telomeres by adding TTAGGG repeats. It consists of a functional RNA component (hTR) which serves as template and a catalytic protein (hTERT) with reverse transcriptase activity. The expression of hTERT alone is sufficient for the immortalisation of cells. Telomerase is highly expressed in tumor cells but at very low level ...
Limitless self-renewal is one of the hallmarks of cancer and is attained by telomere maintenance, essentially through telomerase (hTERT) activation. Transcriptional regulation of hTERT is believed to play a major role in telomerase activation in human cancers. The dominant interest in telomerase results from its role in cancer. The role of telomeres and telomere maintenance mechanisms is well established as a major driving force in generating chromosomal and genomic instability. Cancer cells have acquired the ability to overcome their fate of senescence via telomere length maintenance mechanisms, mainly by telomerase activation. hTERT expression is up-regulated in tumors via multiple genetic and epigenetic mechanisms including hTERT amplifications, hTERT structural variants, hTERT promoter mutations and epigenetic modifications through hTERT promoter methylation. Genetic (hTERT promoter mutations) and epigenetic (hTERT promoter methylation and miRNAs) events were shown to have clinical implications in
Telomeres, the natural ends of linear eukaryotic chromosomes, are essential for chromosome stability. Because of the nature of DNA replication, telomeres require a specialized mechanism to ensure their complete duplication. Telomeres are also capable of silencing the transcription of genes that are located near them. In order to identify genes in the budding yeast Saccharomyces cerevisiae that are important for telomere function, a screen was conducted for genes that, when expressed in high amounts, would suppress telomeric silencing. This screen lead to the identification of the gene TLC1 (telomerase component 1). TLC1 encodes the template RNA of telomerase, a ribonucleoprotein required for telomere replication in a variety of organisms. The discovery of TLC1 confirms the existence of telomerase in S. cerevisiae and may facilitate both the analysis of this enzyme and an understanding of telomere structure and function. ...
Author Summary The enzyme complex telomerase, with its two main components telomerase reverse transcriptase and telomerase RNA, plays an important role in telomere maintenance. Perturbation of telomere length regulation can ultimately result in cellular senescence (telomere shortening) and is also observed in tumor cells (increased telomere maintenance). Recent studies suggest telomerase RNAs can function independently of the telomerase complex and promote tumor development independently of telomere maintenance. Here we demonstrate that vTR, a herpesvirus-encoded telomerase RNA, serves two distinct functions in MDV-induced tumor formation. vTR has its first function early after infection, when it is part of the telomerase complex and contributes to the survival of rapidly dividing transformed cells. The second function of vTR is independent of telomerase action and essential for formation of solid lymphomas and metastasis. This latter function is likely a consequence of vTR-mediated gene regulation that
PARN encodes poly(A)-specific ribonuclease. Biallelic and monoallelic PARN variants are associated with Hoyeraal-Hreidarsson syndrome/dyskeratosis congenita and idiopathic pulmonary fibrosis (IPF), respectively. The molecular features associated with incomplete penetrance of PARN-associated IPF have not been described. We report a family with a rare missense, p.Y91C, and a novel insertion, p.(I274*), PARN variant. We found PARN p.Y91C had reduced deadenylase activity and the p.(I274*) transcript was depleted. Detailed analysis of the consequences of these variants revealed that, while PARN protein was lowest in the severely affected biallelic child who had the shortest telomeres, it was also reduced in his mother with the p.(I274*) variant but telomeres at the 50th percentile. Increased adenylation of telomerase RNA, human telomerase RNA, and certain small nucleolar RNAs, and impaired ribosomal RNA maturation were observed in cells derived from the severely affected biallelic carrier, but not in ...
Telomeres are important protein-DNA structures at the ends of linear eukaryotic chromosomes that are necessary for genome integrity. Telomeres are maintained by intermittent action of telomerase. I explored the kinetics of telomere length homeostasis in the model plant Arabidopsis thaliana by crossing wild type plants to different generations of telomerase deficient plants, and then analyzing telomere length in the resulting progeny. Unexpectedly, I found plants lacking telomerase for seven generations can lengthen telomeres when telomerase is reintroduced, but one generation is not sufficient to reestablish the telomere set point. Est1 is a non-catalytic component of the Saccharomyces cerevisiae telomerase holoenzyme. To investigate the role of Est1 in higher eukaryotes, I identified two putative Est1 homologues in Arabidopsis, AtEST1a and AtEST1b. Plants deficient in AtEST1a displayed no vegetative or reproductive defects. However, plants deficient for AtEST1b were sterile and had severe ...
TY - JOUR. T1 - Telomere length and physical performance among older people - the Helsinki Birth Cohort Study. AU - Åström, Max J.. AU - von Bonsdorff, Mikaela B.. AU - Perälä, Mia-Maria. AU - Salonen, Minna K.. AU - Rantanen, Taina. AU - Kajantie, Eero. AU - Simonen, Mika. AU - Pohjolainen, Pertti. AU - Haapanen, Markus J.. AU - Guzzardi, Maria A.. AU - Iozzo, Patricia. AU - Kautiainen, Hannu. AU - Eriksson, Johan G.. PY - 2019/10. Y1 - 2019/10. KW - 3142 Public health care science, environmental and occupational health. KW - Biomarkers. KW - Physical function. KW - Aging. KW - Epidemiology. KW - Biomarkers. KW - Physical function. KW - Aging. KW - Epidemiology. KW - MORTALITY. KW - ASSOCIATION. KW - FRAILTY. KW - BIOMARKERS. KW - DISABILITY. KW - CAPABILITY. KW - FITNESS. KW - MARKERS. KW - HEALTH. KW - BLOOD. U2 - 10.1016/j.mad.2019.111145. DO - 10.1016/j.mad.2019.111145. M3 - Article. VL - 183. JO - Mechanisms of Ageing and Development. JF - Mechanisms of Ageing and Development. SN - ...
Postdoctoral position to study telomere structure and function. A postdoctoral position is available to investigate telomere dynamics in Saccharomyces cerevisiae in the laboratory of Art Lustig at Tulane University Medical Center. We have had a long-standing fascination in telomere structure and function and are currently focusing on two broad areas: 1) The mechanisms of nucleation and inheritance of telomeric silencing (e.g. MCB 16: 2843); and 2) the mechanism of telomere size maintainence (e.g. Genes Dev. 10: 1310). Candidates should have a background in molecular biology and/or genetics. Background in yeast is preferable but not required. Interested candidates should send their c.v. either by e-mail, fax, or mail to the address listed below. Arthur J. Lustig Associate Professor Department of Biochemistry SL43 Tulane University Medical Center 1430 Tulane Avenue New Orleans, LA 70112 phone: 504-584-3688 fax: 504-584-2739 ...
Knowing that pluripotent embryonic cells are telomerase positive, we could freely draw conclusion that all of them should have similar telomeres length. However, it has been shown that the telomere length in the oocytes and blastocysts differs greatly from the telomeres in the zygote, more than it had been expected [86]. While an average oocytes telomere length has been determined as ~ 11.12 kb and a blastocysts as 12.22 kb, the average telomere length for the cleavage stage embryo is ~ 8.43 kb [87]. It is speculated that the alternative lengthening of telomeres (ALT) mechanism through chromosomal recombination in early embryo cells could yield in this discrepancy [88]. The ALT pathway has not yet been observed in human embryo cells, but it already has been shown that both mechanisms (telomerase-dependent and -independent) coexist in the same cell, which possibly could explain the differential telomeres length phenomenon in the human embryo cells [89,90]. Moreover, it has been reported that ...
The lab studies telomeres, protective elements at the ends of chromosomes that are critical for genome integrity and shorten with cell division. de Lange seeks to understand how telomeres are protected by a protein complex called shelterin, how they are replicated and maintained, and how telomere loss contributes to genome instability in cancer. The lab also studies DNA double-strand break repair with emphasis on the function of two critical DNA repair proteins, BRCA1 and 53BP1. Research in the de Lange lab focuses on human and mouse telomeres, which are made up of long arrays of double-stranded TTAGGG repeats that end in a single-stranded 3′ overhang. The lab identified a six-subunit protein complex, which they named shelterin, that specifically binds to telomeres. Using genetic approaches, de Lange and her colleagues determined the fate of telomeres lacking one or more of the six shelterin subunits. The results showed that cells lacking shelterin perceive their natural chromosome ends as ...
The human Xp/Yp telomere-junction region exhibits high levels of sequence polymorphism and linkage disequilibrium. To determine whether this is a general feature of human telomeres, we have undertaken sequence analysis at the 12q telomere and have extended the analysis at Xp/Yp. A total of 22 single-nucleotide polymorphisms (SNPs) and one 30-bp duplication were detected in the 1,870 bp adjacent to the 12q telomere. Twenty polymorphic positions were in almost complete linkage disequilibrium, creating three common diverged haplotypes accounting for 80% of 12q telomeres in the white population. A further 6% of 12q telomeres contained a 1,439-bp deletion in the DNA flanking the telomere. The remaining 13% of 12q telomeres did not amplify with the primers used (nulls). The distribution of telomere (TTAGGG) and variant repeats within 12q telomeres was hypervariable, but alleles with similar distribution patterns were associated with the same haplotype in the telomere-adjacent DNA. These data suggest ...
In recent years it has become increasingly clear that articular cartilage harbours a viable pool of progenitor cells and interest has focussed on their role during development and disease. Analysis of progenitor numbers using fluorescence-activated sorting techniques has resulted in wide-ranging estimates, which may be the result of context-dependent expression of cell surface markers. We have used a colony-forming assay to reliably determine chondroprogenitor numbers in normal and osteoarthritic cartilage where we observed a 2-fold increase in diseased tissue (P , 0.0001). Intriguingly, cell kinetic analysis of clonal isolates derived from single and multiple donors of osteoarthritic cartilage revealed the presence of a divergent progenitor subpopulation characterised by an early senescent phenotype. Divergent sub-populations displayed increased senescenceassociated β-galactosidase activity, lower average telomere lengths but retained the capacity to undergo multi-lineage differentiation. ...
Our lab is interested in telomere function, the regulation of telomere length and the biochemistry of telomerase. Telomeres are essential for both chromosome stability and for length maintenance. Telomerase is a ribonucleoprotein reverse transcriptase that synthesizes telomere repeats onto chromosome ends. Telomerase is required for telomerase length maintenance: in the absence of telomerase, telomeres shorten progressively. To understand the telomerase, we initially focused on the well characterized Tetrahymena enzyme. We extensively characterized the functional regions of the Tetrahymena telomerase RNA. Using a reconstitution system, we mapped the essential RNA functional region. To extend this analysis to mammalian telomerase we established the secondary structure of the vertebrate telomerase RNA. We cloned and sequenced telomerase RNA genes from 35 vertebrate species and determined the secondary structure using phylogenetic comparative analysis. We identified four highly conserved domains in ...
A new study reported in the press this week looks at the relationship of exercise to expression of telomerase and telomere lengths in athletes and non-athletes. Other studies on the same topic have appeared in the last year or so. My purpose here is to review these studies in the context of some earlier studies. It is not just a simple matter of the more and the harder the exercise, the better.. The 12th theory of aging in my treatise Telomere Shortening and Damage forwards the hypothesis that longer telomere lengths are likely to be correlated with longer lifespans and that keeping ones telomeres as long as possible through expression of telomerase is vital for health and longevity. I have devoted numerous blog entries to telomeres and telomerase, including most recently Timely telomerase tidbits, Breakthrough telomere research finding, and Telomere and telomerase writings. On the other hand, it is also well established that regular exercise is also strongly supportive of ...
Telomere Binding Activity (TBA), an abundant protein from Saccharomyces cerevisiae, was identified by its ability to bind to telomeric poly(C1-3A) sequence motifs. The substrate specificity of TBA has been analyzed in order to determine whether the activity binds to a unique structure assumed by the …
(2016) Biron-Shental et al. Placenta. Objective Diabetes during pregnancy causes an intrauterine environment that influences lifetime sickness of the mother and the fetus. There is a correlation between diabetes and telomere shortening; however, very little is known about telomere homeostasis in ...
In almost all eukaryotes, the task of solving the end-replication problem and counteracting telomere erosion is assigned to the telomerase enzyme complex (Greider and Blackburn, 1985). The active telomerase holoenzyme in mammalian cells exists as a dimer and consists of the telomerase reverse transcriptase (TERT), the telomerase RNA component (TERC) and dyskerin (Cohen et al., 2007). In humans, telomerase is expressed during the early stages of embryogenesis, and its expression is subsequently repressed in most somatic cells, except the male germ line, activated lymphocytes and stem cells found in certain regenerative tissues (Wright et al., 1996). Furthermore, the vast majority of human cancer cells reactivate telomerase, and are thus capable of proliferating indefinitely (Kim et al., 1994). Regulation of telomerase is primarily exerted at the level of TERT transcription. Extensive analysis of the promoter region has uncovered many transcriptional binding sites and regulatory elements, ...
Fig. 3. NHP2 mutations result in short telomeres and reduced TERC levels. (A) Telomere length measurements in 112 healthy control subjects (open circles) are plotted against age with a line of best fit. Members of families in which NHP2 mutations are segregating are shown as gray triangles (Y139H heterozygotes), a black triangle (Y139H homozygote), gray square (V126M heterozygote), gray diamond (X154R heterozygote), black diamond (V126M/X154R, compound heterozygote), and open diamond (normal sibling). (B) Age-adjusted telomere lengths (delta tel, the difference between the observed telomere length and the length expected from the line of best fit drawn in panel a) for healthy control subjects (open circles, n = 112), NHP2 family members (as in A), and patients with dyskerin mutations (dashes, n = 67). (C) TERC levels, expressed as a TERC/ABL ratio, in healthy control individuals (open circles, n = 24), NHP2 family members (as in A), and patients with dyskerin mutations (dashes, n = 27). ...
The mechanism of telomere elongation by telomerase. In this example the telomerase enzyme is synthesizing the repeated sequence TTGGGG, which is the telomeric sequence of Tetrahymena thermophila.. The first detection of telomerase activity, in the ciliateTetrahymena thermophila, was followed by its detection in a variety of organisms including vertebrates, yeast, and plants. In the absence of telomerase activity, telomeres shorten with each cell division. Normal human somatic cells lack detectable telomerase activity, whereas telomerase is activated in germ cells, immortalized cells and the majority of primary tumors. The correlation between telomerase activity and tumor growth has spurred investigations of the possiblities to use telomerase activity as a target for anticancer drug treatments.. Our identification of much longer telomeric repeat units (16-26 bp) in several yeast species has expanded the previous range of telomeric repeat sequences to include not only more complex sequences, but ...
Mutations in the gene for telomerase reverse transcriptase (hTERT) are associated with diseases including dyskeratosis congenita, aplastic anemia, pulmonary fibrosis and cancer. Understanding the molecular basis of these telomerase-associated diseases requires dependable quantitative measurements of telomerase enzyme activity. Furthermore, recent findings that the human POT1-TPP1 chromosome end-binding protein complex stimulates telomerase activity and processivity provide incentive for testing variant telomerases in the presence of these factors. In the present work, we compare multiple disease-associated hTERT variants reconstituted with the RNA subunit hTR in two systems (rabbit reticulocyte lysates and human cell lines) with respect to telomerase enzymatic activity, processivity and activation by telomere proteins. Surprisingly, many of the previously reported disease-associated hTERTalleles give near-normal telomerase enzyme activity. It is possible that a small deficit in telomerase activity is
In the new paper published in Nature Communications, the group of Gian Paolo Dotto describes the central role of CSL in telomere homeostasis of dermal fibroblasts with important implications for genomic instability of cancer stromal cells
See related article, pp 420-425. The discovery that critical telomere shortening initiates replicative senescence triggered a vast body of epidemiological studies exploring its implications for human aging. These studies demonstrated that telomeres-typically measured in the DNA isolated from blood cells-clearly shorten with age. On average, shorter telomeres were found in subjects with atherosclerosis and independently predicted atherosclerotic cardiovascular disease (ACVD)-associated mortality. Moreover, Mendelian randomization studies point to a causal role for shorter telomere length in ACVD, lending support to the hypothesis that the protective antitumor mechanism elicited by critical telomere attrition may act at the expense of unsuccessful cardiovascular aging.1 Yet, consensus is lacking on the mechanism underlying the presumed associations between shorter telomeres, atherosclerosis, and ACVD. This problem was addressed in the epidemiological research by Toupance et al,2 published in the ...
Telomerase activity is restricted in humans. Consequentially, telomeres shorten in most cells throughout our lives. Telomere dysfunction in vertebrates has been primarily studied in inbred mice strains with very long telomeres that fail to deplete telomeric repeats during their lifetime. It is, therefore, unclear how telomere shortening regulates tissue homeostasis in vertebrates with naturally short telomeres. Zebrafish have restricted telomerase expression and human-like telomere length. Here we show that first-generation tert(-/-) zebrafish die prematurely with shorter telomeres. tert(-/-) fish develop degenerative phenotypes, including premature infertility, gastrointestinal atrophy, and sarcopaenia. tert(-/-) mutants have impaired cell proliferation, accumulation of DNA damage markers, and a p53 response leading to early apoptosis, followed by accumulation of senescent cells. Apoptosis is primarily observed in the proliferative niche and germ cells. Cell proliferation, but not apoptosis, is ...
Telomerase, a ribonucleoprotein with reverse transcriptase activity, enables human cells to maintain chromosomal stability and to proliferate without limits. Various stud..
Telomerase activity is involved in telomere length maintenance. Leukocytes, unlike many human somatic tissues, have detectable telomerase activity. These cells provide a normal human cell type in which to study telomerase. We studied the regulation of telomerase activity and the telomerase RNA component as leukocytes were stimulated to enter the cell cycle. In primary human leukocytes stimulated with phytohemagglutinin, telomerase activity increased , 10-fold as naturally quiescent cells entered the cell cycle. Antibodies to the T cell receptor (TCR)/CD3 complex and the costimulatory CD28 receptor induced telomerase activity in a T cell-enriched population of cells. Rapamycin, an immunosuppressant that blocks TCR/CD3 signal transduction pathways and cdk2 activation, blocked telomerase induction. Hydroxyurea, an inhibitor of S phase, did not block cdk2 kinase activity or telomerase activation. In summary, telomerase is regulated in G1 phase as normal human T cells enter the cell cycle.. ...
We sought to examine the relationship between elevated transferrin saturation (TS) and measures of health status (telomere length and patient-reported health-related quality of life) to assess whether elevated TS is associated with negative patient outcomes beyond increased risk for morbidity and mortality, using a cross-sectional analysis of the Hemochromatosis and Iron Overload Screening Study supplemented with assays for leukocyte telomere length in adults ≥25 years old (n = 669). Among individuals with elevated TS (≥45 % for women and ≥50 % for men), who also had a usual source of care, only 5.2 % reported ever being told by a doctor that they had an elevated iron condition. In a fully adjusted general linear regression model controlling for demographic characteristics as well as health conditions associated with iron overload, elevated TS versus non-elevated TS was associated with worse general health status (60.4 vs. 63.8, P , 0.05), mental health status (76.5 vs. 82.2, P , 0.0001) ...
To find an answer, the team started a long-tem study on changes in telomere length. In the Vienna Woods in Austria they regularly checked 130 nest-boxes that are occupied by free-living dormice. The researchers collected the rodents buccal mucosa for three years. Thus, they could extract the DNA and determine the relative telomere length for each dormouse individually using qPCR. With this method scientists can define the amount of target DNA compared to a reference gene of the same sample.. Elongation does not only occur, it even increases in older edible dormice. We found out that the telomeres were shortened in young animals but length significantly increased once the dormice were six years old or older. To top it all, the rate of telomere elongation also increased with increasing age of the dormice, says Franz Hoelzl.. Among the variables tested, only age significantly affected RTL in a non-linear pattern with telomere length decreasing in younger and increasing in older dormice. Hoelz ...
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Recent work has yielded considerable information concerning the structure and function of telomeres and their associated sequences in the budding yeast Saccharomyces cerevisiae. The structure and maintenance of telomeres depends not only on the RNA template and the catalytic subunit of telomerase, b …
Telomerase activity has been regarded as a critical step in cellular immortalization and carcinogenesis and because of this, regulation of telomerase represents an attractive target for anti-tumor specific therapeutics. Recently, one avenue of cancer research focuses on antisense strategy to target the oncogenes or cancer driver genes, in a sequence specific fashion to down-regulate the expression of the target gene. The protein catalytic subunit, human telomerase reverse transcriptase (hTERT) and the template RNA component (hTERC) are essential for telomerase function, thus theoretically, inhibition of telomerase activity can be achieved by interfering with either the gene expression of hTERT or the hTERC of the telomerase enzymatic complex. The present study showed that phosphorothioate antisense oligonucleotide (sASO)-nuclear localization signal (NLS) peptide conjugates targeting hTERC could inhibit telomerase activity very efficiently at 5 μM concentration but less efficiently at 1 μM ...
Objective: Studies in white people have shown that telomere length, a marker of biological ageing, is shorter in individuals with coronary artery disease (CAD). South Asian Indians have a high prevalence of CAD, especially premature CAD. We examined the association of telomere length with CAD in Indian subjects.. Design: Case-control study.. Setting: Mumbai, India.. Subjects: 238 consecutive patients (aged 29-82 years), admitted to Cumballa Hill Hospital for coronary investigations or treatment and 238 control subjects (aged 30-87 years) from the same area without any clinical evidence of CAD.. Methods: Mean leucocyte telomere length was measured using a polymerase chain reaction (PCR)-based assay and expressed as a ratio (T/S ratio) of the telomere signal to that of a control single copy gene.. Results: T/S ratio was significantly lower in CAD cases compared with controls (cases 1.21 (95% CI 1.16 to 1.26); controls 1.33 (1.28 to 1.38); p = 0.0003), equivalent to approximately 166 base pairs. ...
Fusion of critically short or damaged telomeres is associated with the genomic rearrangements that support malignant transformation. We have demonstrated the fundamental contribution of DNA ligase 4-dependent classical non-homologous end-joining to long-range inter-chromosomal telomere fusions. In contrast, localized genomic recombinations initiated by sister chromatid fusion are predominantly mediated by alternative non-homologous end-joining activity that may employ either DNA ligase 3 or DNA ligase 1. In this study, we sought to discriminate the relative involvement of these ligases in sister chromatid telomere fusion through a precise genetic dissociation of functional activity. We have resolved an essential and non-redundant role for DNA ligase 1 in the fusion of sister chromatids bearing targeted double strand DNA breaks that is entirely uncoupled from its requisite engagement in DNA replication. Importantly, this fusogenic repair occurs in cells fully proficient for non-homologous ...
The foundational understanding of the role of telomeres and telomerase in disease has been rooted in curiosity-driven science, in simple systems and model organisms (22). One major theme that emerges at the intersection between this fundamental science and disease genetics is that relatively small, subtle changes affecting telomerase abundance or function can influence telomere length and, in turn, disease risk (23). The exquisite sensitivity of telomere length to these small changes is related to the fact that telomerase is in very low abundance and its activity is tightly regulated. In yeast, mice, and humans, the number of telomere ends exceeds the number of telomerase molecules (refs. 24, 25, and reviewed in refs. 23, 26). The low levels of telomerase set up a system wherein not all telomeres are elongated during a given cell cycle even when telomerase is normally expressed (27). There are at least three additional limits on telomerase activity. The first is that the essential telomerase ...
Dyskeratosis congenita (DC) is an inherited bone marrow failure syndrome characterized by the presence of short telomeres at presentation. Mutations in ten different genes, whose products are involved in the telomere maintenance pathway, have been shown to cause DC. The X-linked form is the most common form of the disease and is caused by mutations in the gene DKC1, encoding the protein dyskerin. Dyskerin is required for the assembly and stability of telomerase and is also involved in ribosomal...
longest telomeres. Telomeres also exist as a possible drug target. While telomeres serve a vital function in humans, telomerase ... Although leukocyte telomeres shorten with age, sperm telomeres lengthen with age. Shorter telomeres are theorized to impose ... These function in both telomere maintenance and capping. Telomeres form large loop structures called telomere loops, or T-loops ... At the very end of the T-loop, the single-stranded telomere DNA is held onto a region of double-stranded DNA by the telomere ...
... , also known as protelomerase, is an enzyme found in bacteria which contain linear plasmids. In order to ... Telomere resolvase then cuts the structure and reforms the hairpin turns, forming two new, identical linear plasmids. Shi, Ke; ... Huang, Wai Mun; Aihara, Hideki (2013). "An enzyme-catalyzed multistep DNA refolding mechanism in hairpin telomere formation". ...
A telomere is a region of repetitive nucleotide sequences at each end of a chromosome. Telomere may also refer to: Telomere ( ... Telomerization This disambiguation page lists articles associated with the title Telomere. If an internal link led you here, ... insect morphology), a type of genital clasper Telomere resolvase, an enzyme found in bacteria which contain linear plasmids. ...
A mega-telomere (also known as an ultra-long telomere or a class III telomere), is an extremely long telomere sequence that ... Telomeres are identified by telomere arrays. A telomere array is a unique arrangement of telomeres within a sample (cell, ... Telomere shortening). While the chromosomes in most eukaryotic organisms are capped with telomeres, mega-telomeres are only ... Like regular telomeres, mega-telomeres are made of a repetitive sequence of DNA and associated proteins, and are located on the ...
... s not present may cause the exposed telomeres to undergo a DNA repair response, having mistakenly ... Telomere-binding proteins can generate a T-loop to protect chromosome ends. TRFs are double-stranded proteins which are known ... Telomere-binding proteins function to generate a T-loop, which is a specialized loop structure to cap the telomeric ends. ... By targeting the telomere-binding proteins which serve to protect the ends, it may prove fruitful in future drug therapy. ...
A telomere (pl.; telomeres or telomeron), literally "end piece", is a term in insect morphology, and refers to a type of " ... The telomere may have sensilla.[citation needed] Present in higher insect orders from Orthoptera to Hymenoptera. In adult ... insects of these orders, genital claspers may develop in two segments, a proximal basimere and a distal telomere. v t e ( ...
... is a protein that in humans is encoded by the RIF1 gene. RIF1 and RIF2 cap the chromosome ends ... v t e (Articles with short description, Short description is different from Wikidata, Genes on human chromosome 2, Telomere- ... "Entrez Gene: RIF1 RAP1 interacting factor homolog (yeast)". Ribeyre C, Shore D (2012). "Anticheckpoint pathways at telomeres in ... Xu L, Blackburn EH (December 2004). "Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules ...
Importantly, because telomeres are highly repetitive, invasion between or within telomeres is not limited by the requirement ... The main alternative lengthening mechanism for telomeres is a type of homologous recombination called Break-induced Telomere ... this mechanism is used to extend telomeres. Because telomeres are by nature repetitive, matching sequences are widely available ... Alternative Lengthening of Telomeres (also known as "ALT") is a telomerase-independent mechanism by which cancer cells avoid ...
They then used α factor to block cells with induced short telomeres in late G1 phase and measured the change in telomere length ... telomere-shortening every S phase. Measurements of telomere lengths across cell types at various ages suggest that this gradual ... Almost all cancer cells have shortened telomeres. This may seem counter-intuitive, as short telomeres should activate the ATR/ ... cancer cells have short telomeres because they progress through an intermediate stage of telomere shortening-caused by division ...
"Telomere-to-Telomere". NHGRI. Retrieved 2022-08-16. Nurk S, Koren S, Rhie A, Rautiainen M, Bzikadze AV, Mikheenko A, et al. ( ... In 2022, the Telomere-to-Telomere (T2T) Consortium published the first completely assembled reference genome (version T2T-CHM13 ... It presents gaps mostly in areas concerning telomeres, centromeres and long repetitive sequences, being the biggest gap along ...
Again, it can be presumed that a reduction in TERC results in aberrant telomere maintenance and thus shortened telomeres. Those ... the telomere, during development. Telomeres are placed by telomerase on both ends of linear chromosomes as a way to protect ... Dyskeratosis congenita is a disorder of poor telomere maintenance mainly due to a number of gene mutations that give rise to ... March 2010). "Telomere elongation in induced pluripotent stem cells from dyskeratosis congenita patients". Nature. 464 (7286): ...
They examined the telomeres and telomerase in women. Their results indicated that doctors could monitor telomere length and ... The Telomere Effect: A Revolutionary Approach to Living Younger, Healthier, Longer. While studying telomeres and the ... Since telomeres shorten with every division of a cell, replenishing these caps is essential to long-term cell growth. Through ... The Telomere Effect: the New Science of Living Younger (2017) "Carmel High graduate named to National Academy of Medicine". The ...
... end of telomeres. A telomere is a region of repetitive sequences at each end of the chromosomes of most eukaryotes. Telomeres ... Telomerase reverses telomere shortening. Telomerase restores short bits of DNA known as telomeres, which are otherwise ... Cherif H, Tarry JL, Ozanne SE, Hales CN (March 2003). "Ageing and telomeres: a study into organ- and gender-specific telomere ... A comparative biology study of mammalian telomeres indicated that telomere length of some mammalian species correlates ...
Telomeres When telomeres of chromosomes shorten with continued cell divisions, the chromosome ends may also fuse, forming ... Chromosomal inversion Telomeres Cytogenetics Nuclear radiation Intellectual disorders Nussbaum, Robert; McInnes, Roderick; ... Boukamp, Petra; Popp, Susanne; Krunic, Damir (2005-11-01). "Telomere-Dependent Chromosomal Instability". Journal of ...
Telomere is a mysterious terrorist organization that is behind the attacks on The Bund. Katie Maurice A female vampire who ... It is later revealed that he is a mole for Telomere. The Eight Elite consists of the best hunters in the Earth Clan. Each ... Hysterica had a habit of referring to her slaves as "Pigs." In the anime, she worked for Telomere, but still tried to contact ... In the anime, it is heavily suggested one or all of them are controlling Telomere, a terrorist group created to kill Mina. Also ...
Located in Madrid, it provides telomere diagnostics, based on a technology, known as TAT (Telomere Analysis Technology) as well ... even when telomeres are short. Therefore, alterations in telomere length have great potential as a biomarker in cancer. ... Length of Telomeres, and the Role of Experiential Avoidance and Compassion Prenatal Undernutrition and Leukocyte Telomere ... Many studies link long telomeres and a slower rate of telomere shortening with greater longevity. For example, research done on ...
Gomes, Nuno M. V.; Shay, Jerry W.; Wright, Woodring E. (2010). "Telomere biology in Metazoa". FEBS Letters. 584 (17): 3741-3751 ...
Telomere Cairns, John (1975). "Mutation selection and the natural history of cancer". Nature. 255 (5505): 197-200. Bibcode: ...
"Entrez Gene: POT1 POT1 protection of telomeres 1 homolog (S. pombe)". Bauman P, Carolyn P (2010). "Pot1 and telomere ... POT1 is required for telomere protection because it allows for telomere inhibition of DNA damage response factors. The protein ... that binds to the TTAGGG repeats of telomeres, regulating telomere length and protecting chromosome ends from illegitimate ... Protection of telomeres protein 1 is a protein that in humans is encoded by the POT1 gene. This gene is a member of the ...
i.e., telomere length variation); epigenomics/epigenetics, organismal and corresponding cell specific transcriptomic regulating ...
In 1999 it was reported that telomeres, which cap the end of chromosomes, terminate in a lariat-like structure termed a T-loop ... Griffith, J. D.; Comeau, L.; Rosenfield, S.; Stansel, R. M.; Bianchi, A.; Moss, H.; De Lange, T. (1999). "Mammalian telomeres ... Greider, C. W. (1999). "Telomeres do D-loop-T-loop". Cell. 97 (4): 419-422. doi:10.1016/s0092-8674(00)80750-3. PMID 10338204. ... Maestroni L, Matmati S, Coulon S (2017). "Solving the Telomere Replication Problem". Genes. 8 (2): E55. doi:10.3390/ ...
January 2014). "Enhanced telomere rejuvenation in pluripotent cells reprogrammed via nuclear transfer relative to induced ... Thus, reprogramming leads to the restoration of embryonic telomere length, and hence increases the potential number of cell ... It was found that reprogramming leads to telomere lengthening and subsequent shortening after their differentiation back into ... West MD, Vaziri H (July 2010). "Back to immortality: the restoration of embryonic telomere length during induced pluripotency ...
Author of The Telomere (1995). Professor Thomas Burton Loram Kirkwood CBE (1951-) Dr James Brown (1975-)Elected to membership ( ...
The study was halted early, after telomere attrition was reduced in all 12 patients who could be evaluated. 12 of 27 patients ... A 2016 phase I/II prospective study orally administered 800 mg per day to 27 patients with telomere diseases. The primary ... May 2016). "Danazol Treatment for Telomere Diseases". The New England Journal of Medicine. 374 (20): 1922-1931. doi:10.1056/ ... efficacy endpoint was a 20% reduction in the annual rate of telomere attrition measured. Toxic effects formed the primary ...
When that chromosome subsequently replicates it forms two sister chromatids which both lack a telomere. Since telomeres appear ... Since the two resulting chromatids lack telomeres, when they replicate the BFB cycle will repeat, and will continue every ... The BFB cycle begins when the end region of a chromosome, called its telomere, breaks off. ... Murnane, John P. (2012). "Telomere dysfunction and chromosome instability". Mutation Research. 730 (1-2): 28-36. doi:10.1016/j. ...
Telomeres are regions of repetitive DNA at the end of a chromosome, which provide protection from chromosomal deterioration ... Most of the highly repetitive DNA is found in centromeres and telomeres (see above) and most of it is functional although some ... The genome also contains telomere sequences and centromeres as expected. Much of the repetitive DNA seen in other eukaryotes ... Recent studies have shown that telomeres function to aid in its own stability. Telomeric repeat-containing RNA (TERRA) are ...
In plants, the telomere sequence is conserved, which implies that this strategy can be utilized to successfully construct ... Yu, W.; Lamb, J. C.; Han, F.; Birchler, J. A. (2006). "Telomere-mediated chromosomal truncation in maize". Proceedings of the ... A minichromosome is a small chromatin-like structure resembling a chromosome and consisting of centromeres, telomeres and ... The minimum constituent parts of a chromosome (centromere, telomeres, and DNA replication sequences) are assembled by using ...
Another example related to aging is the Telomere theory. Telomere theory proposes that telomeres shorten with repeated cell ... However, there is still the question whether telomere length causes these diseases or if the diseases cause shortened telomeres ... Telomere shortening is common in somatic cells. However, germ line and stem cells prevent the end replication problem with the ... The trade-off exists as the cell benefits from telomerase which prevents permanent growth arrest but telomere shortening is ...
Telomeres form the terminal region of mammalian chromosomes and are essential for stability and aging and play central roles in ... Telomeres have been long considered transcriptionally inert DNA-protein complexes until it was shown in the late 2000s that ... These ncRNAs are heterogeneous in length, transcribed from several sub-telomeric loci and physically localise to telomeres. ... Blasco MA (October 2007). "Telomere length, stem cells and aging". Nature Chemical Biology. 3 (10): 640-649. doi:10.1038/ ...
Telomere loss can be lethal for many cells, but in the few that are able to restore the expression of telomerase can bring ... Telomeres - which are a protective 'cap' at the end of DNA molecules - normally shorten in each replication cycle. In certain ... However, telomere degeneration can also induce tumorigenesis in other cells. The key difference is the presence of a functional ... Telomere shortening and p53 expression is a key mechanism to prevent uncontrolled replication and tumor development because ...
Studying telomeres, the structures that protect the ends of chromosomes, has become a key issue in biology. In recent years, ... Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect ... Researchers have shown that it is possible to extend the life of mice by generating hyper-long telomeres, without using any ... For the first time, researchers have found a link between long telomeres and an increased risk for colorectal cancer, according ...
Whether telomere length is a marker of biological aging or a cause of it remains to be seen. But limiting. the factors that are ... Special structures called telomeres keep a close eye on the damage that accumulates in our cells and signal when it is time for ... Once telomere length reaches a particular cut-off point, the cell becomes senescent, meaning that it can no longer divide and ... Telomeres are stretches of DNA and proteins at the ends of our chromosomes. Each time a cell divides, these stretches naturally ...
... therapies to curb telomere shortening may prevent dementia. ... Study results suggest that if telomere length determines aging ... Cancer researchers are studying the impact of telomere loss on cancer risk. It appears that telomere shortening may be a ... "If telomere shortening is truly an important part of the pathogenetic process of aging and not simply some sort of marker of ... Telomere length (TL) is likely influenced by genetic factors, as well as by factors such as smoking, diet, and physical ...
In this process, the telomere itself shortens with each cell division and can consequently be t … ... Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving ... Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of ... Telomeres, early-life stress and mental illness Adv Psychosom Med. 2015;34:92-108. doi: 10.1159/000369088. Epub 2015 Mar 30. ...
Get Big Think for Your Business. Enable transformation and drive culture at your company with lessons from the biggest thinkers in the world ...
Read stories, features and news related to telomere. ... Researchers at Duke University studied the telomeres - the tip ... Shortly after the therapy, the aged cells started dividing and had longer telomeres. ... Scientists discovered that having children significantly shortened telomeres (genetic markers of aging). ...
Telomeres are a protective nucleoprotein structure at each chromosome end. Telomeres naturally shorten with age. The telomere ... Telomere Mean and Standard Deviation (Surplus) (TELO_A) Data File: TELO_A.xpt First Published: November 2014. Last Revised: ... It is important to note that there is wide variance in telomere length measures across labs and types of assays. While they ... While comparisons across studies of telomere length in base pairs are commonly done, it is not highly accurate. ...
List of Publications - arranged by topics. In the following lists the publications are arranged according to their contents. If you want to read the papers, go to publication index and select the corresponding year. There you can find the relevant pdfs.. ...
Could telomeres provide an answer to questions like "How long will I live?" or "Will I get cancer?" What are telomeres? ... Tell Me More about Telomeres. Researchers, journalists, and inquiring minds want to know more about telomeres, which seem to ... Telomeres are structures at the ends of chromosomes that contain repetitive stretches Read More , ...
Their joint work led them to realize that TERRA actually accumulates at all telomeres, but at long telomeres it is rapidly ... Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from ... When a telomere accidentally gets cut short early in a cells lifetime, it needs to be fixed so that the cell doesnt become ... Therefore, telomere shortening is a double-edged sword and has to be carefully regulated to strike a balance between ageing and ...
... Applicators in the Agricultural Health Study. ... BACKGROUND: Telomere length (TL) in surrogate tissues may be influenced by environmental exposures. OBJECTIVE: We aim to ... Relative telomere length (RTL) was measured using quantitative real-time PCR. Linear regression modeling evaluated the ... Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study. - ...
... understanding and potentially treating human diseases caused by mutations in genes that control both the ribosome and telomere. ... The findings show a clear genetic link between components of ribosome biogenesis pathway and telomere length, mapping a new ... Telomeres are the physical ends of chromosomes and they shorten with age in most cells. Accelerated shortening of telomeres is ... CNIO researchers obtain the first mice born with hyper-long telomeres. Mice with hyper-long telomeres live, on average, 13% ...
The Telomere blog clearly explains why most of disease can be explained by telomere erosion ... In the telomere blog, we learn that most research assumes everything ages at the same rate but a simple thought experiment ... In this weeks exosome blog, we review the possible impact of MSC exosomes on aging…in the telomere blog, we review a case of a ... This weeks archives: I address the common question "what is the difference between stem cells and exosomes?…..The telomere blog ...
Common variants near TERC are associated with mean telomere length ... Individuals are born with telomeres of certain length and in many cells telomeres shorten as the cells divide and age. Telomere ... Gene Variant Associated with Telomere Length a Target for Life Extension Treatment. April 7, 2017. February 10, 2010. by Brian ... "In this study what we found was that those individuals carrying a particular genetic variant had shorter telomeres i.e. looked ...
Telomere length is an important biomarker in a number of diseases, including male infertility. A decreased telomere length has ... Several studies reported shortening of sperm telomeres associated with infertility. Thus, sperm telomere length can be used as ... Offsprings leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet. 4(e37)2008.PubMed/NCBI View ... Divergence of sperm and leukocyte age-dependent telomere dynamics: Implications for male-driven evolution of telomere length in ...
Infants have long telomeres and adults have shorter telomeres. As we age, our telomeres get shorter and shorter. With each ... Telomere shortening with age would resume (the cellular clock would start again) and telomere length would be lost as the cells ... Telomeres represent the internal cellular clocks. Seen in the figure, telomeres are at the ends of all chromosomes (marked in ... There telomeres stop shortening and remain at a constant length. Without the shortening of telomeres (without the clock running ...
Shortened Telomeres Predict Cancer. A study following 792 persons for 13 years showed that shortened telomeres predict cancer. ... Telomeres are the caps at the end of chromosomes that protect the DNA between cell divisions. Initially all of the patients of ... anti-aging drugs, cancer, cardiovascular diseases, elongate telomeres, life expectancy, lifestyle changes, modified RNA, ...
They seem to have two classes of telomeres: long telomeres that do not shorten with increasing age and shorter telomeres that ... Telomeres are a piece of DNA at the end of chromosomes, and they protect the other DNA. In many species shortening of telomere ... Els Atema discovered that telomeres of great tits differ from telomeres in humans and other bird species. ... In great tits we used the shorter telomeres as measurement for ageing. We found that great tits that are most successful in ...
Martínez P, Blasco MA (2017). Telomere-driven diseases and telomere-targeting therapies. J Cell Biol 216, 875-887. CNIO ... Progressive shortening of telomeres associated with organism ageing leads to ageing. When telomeres are altered, adult stem ... Testing telomerase gene therapy in telomere syndromes and age-related diseases.. *Role of telomerase and telomeres in adult ... Telomeres and Telomerase Group - Fundación Humanismo y Ciencia. María A. Blasco Group Leader. T +34 917328032 (Ext 3400) ...
Telomere length shortens with age. Progressive shortening of our telomeres leads to cell death or transformation into cancer, ... Telomere length shortens with age. Progressive shortening of our telomeres leads to cell death or transformation into cancer, ... Republishing "Telomeres: Cap It All Off with Diet". × Terms You may republish this material online or in print under our ... no wonder lifelong low cholesterol levels have been related to longer telomeres and a smaller proportion of short telomeres-in ...
Somatic cells generally do not maintain telomere sequences, and these cells become senescent in adults as telomeres shorten to ... We show that somatic telomere maintenance is different in asexual and sexual animals. Asexual animals maintain telomere length ... Here we study the telomere biology of planarian flatworms with apparently limitless regenerative capacity fueled by a ... Asexual adult planarian stem cells appear to maintain telomere length over evolutionary timescales without passage through a ...
Telomere and telomere expression data used in the manuscript. (1) Cross sectional and (2) longitudinal data on frillneck ... lizards telomere length in relation to sex, age, survival and temporal change in telomere length. (3) Telomere length (TL) in ... that is lizards with short initial telomeres were subjected to reduced telomere attrition rates compared to lizards with long ... Data from: Curvilinear telomere length dynamics in a squamate reptile. Ujvari, Beata, Deakin University ...
AA grant support: NIH: Human Telomere Genetics R01AG20132; Telomeres & Vascular Aging, R01AG21593; Leukocyte Telomere Dynamics ... Telomere length, telomere-related genes, and breast cancer risk: the breast cancer health disparities study. Genes Chromosomes ... Genetics of leukocyte telomere length and its role in atherosclerosis. Mutat Res 2012;730:68-74. doi:10.1016/j.mrfmmm.2011.05. ... Telomere length in white blood cell DNA and lung cancer: a pooled analysis of three prospective cohorts. Cancer Res 2014;74: ...
In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere ... telomere function, and related DNA damage at least partly through activating the PGC-1,i,α,/i,/TERT pathway. Moreover, ... which is the new link between mitochondria and telomere, was involved in the protective effects of catalpol. Further, by using ... Telomere length is considered as a biomarker of chronological aging [39]. TERT is a key enzyme in regulating telomere length. ...
HOAP is a telomere-binding protein that has a conserved role in Drosophila, but it also needs to evolve quickly to restrict ... 2004) HP1 controls telomere capping, telomere elongation, and telomere silencing by two different mechanisms in Drosophila ... Telomeres: Change and HOAP for the best. HOAP is a telomere-binding protein that has a conserved role in Drosophila, but it ... regulated HTT expression and telomere length. The telomeres in flies carrying the D. yakuba variant did not have the genetic ...
Here we examine the impact of telomere length changes on Arabidopsis thaliana responses to three contrasting abiotic ... Telomere length has been implicated in the organismal response to stress, but the underlying mechanisms are unknown. ... We report that telomere length in wild type and short telomere mutants is resistant to abiotic stress, while elongated ... Telomere length has been implicated in the organismal response to stress, but the underlying mechanisms are unknown. Here we ...
OR long telomere and multiple beta-1 HPV seronegativity = 0.02, 95% CI=0.002- 0.17; OR=0.27 long telomere and multiple beta-1 ... Association between telomere length and SCC, stratified by HPV status, was examined using logistic regression and, odds ratios ... infection and telomere length have both been associated with cutaneous squamous cell carcinoma (SCC). We examined the ... for whom data was available on telomere length and a) beta-HPV serology (135 cases and 201 controls), b) beta-HPV DNA in ...
Website by Zephyrmedia. © Copyright 2022, ARC Centre of Excellence for Coral Reef Studies. ALL RIGHTS RESERVED. ...
Seminars and Events at the Research Institute of Molecular Pathology (IMP) and Vienna Biocenter (VBC).
  • Scientists now know that many factors - including physical exercise , sleep , depression , and certain gene mutations - are associated with reduced telomere length, and, by extension, can lead to premature biological aging. (medicalnewstoday.com)
  • TERC gene mutations lead to telomerase dysfunction, impaired maintenance of telomeres, and reduced telomere length. (medlineplus.gov)
  • Studying telomeres, the structures that protect the ends of chromosomes, has become a key issue in biology. (news-medical.net)
  • Researchers at the Institute of Molecular Biology and Johannes Gutenberg University Mainz have further uncovered the secrets of telomeres, the caps that protect the ends of our chromosomes. (news-medical.net)
  • Telomeres, the repetitive sequences of DNA at the ends of linear chromosomes, have an important function: They protect vulnerable chromosome ends from molecular attack. (news-medical.net)
  • Telomeres are stretches of DNA and proteins at the ends of our chromosomes. (medicalnewstoday.com)
  • Telomeres are structures of tandem TTAGGG repeats that are found at the ends of chromosomes and preserve genomic DNA by serving as a disposable buffer to protect DNA termini during chromosome replication. (nih.gov)
  • Telomeres protect the ends of our chromosomes, much like the plastic cap at the end of a shoelace that prevents the lace from unravelling. (uni-mainz.de)
  • however, telomeres and TERRA are found across all organisms with linear chromosomes. (uni-mainz.de)
  • What we studied are structures called telomeres which are parts of one's chromosomes. (nextbigfuture.com)
  • Telomeres are the caps at the end of chromosomes that protect the DNA between cell divisions. (nethealthbook.com)
  • Telomeres are nucleoprotein complexes located at the ends of chromosomes and are essential for chromosome protection and genomic stability. (cnio.es)
  • Telomeres are specialized structures that 'cap' and protect the ends of linear chromosomes. (elifesciences.org)
  • Losing telomeres leads to harmful anomalies, such as chromosomes fusing together: these structures are therefore conserved in all organisms with linear chromosomes, including (but not limited to) all animals, plants, insects and fungi ( de Lange, 2018 ). (elifesciences.org)
  • Telomeres are random repeat DNA sequences that form a protective cap in the ends of eukaryotic chromosomes. (exposed-skin-care.net)
  • Telomeres consist of repetitive nucleoprotein tracts of sequence (TTAGGG)n that cap the ends of linear chromosomes. (researchsquare.com)
  • It's very important to make sure that our chromosomes don't get damaged to prevent diseases like cancer, and telomeres come to the rescue in this regard. (hackyourgut.com)
  • Telomeres are little protective caps on the ends of chromosomes that prevent deterioration or fusion of frayed ends of DNA. (hackyourgut.com)
  • In light of the importance of telomeres in tissue regeneration, aging, and cancer, the authors decided to analyze the changes that occur in these protective structures of the chromosomes during the "in vivo" reprogramming process, which leads to de-differentiation of the tissues. (bioquicknews.com)
  • Telomeres are highly regulated and dynamic complexes that protect the genomic DNA and prevent the end of linear chromosomes from being misrecognized as a broken DNA. (imrpress.com)
  • Telomerase is a reverse transcriptase capable of compensating telomere attrition by adding telomere repeats to the ends of chromosomes. (imrpress.com)
  • Telomeres are short stretches of DNA are the ends of chromosomes and are essential for fidelity of genetic information during cell division. (2minutemedicine.com)
  • The chromosomes of the DNA have ends that are called telomeres. (healthymoneyvine.com)
  • The Nobel winner says keeping telomeres - the ends of our chromosomes - in prime condition can stave off diseases associated with ageing. (healthymoneyvine.com)
  • Telomeres are repetitive ribonucleoprotein complexes present at ends of chromosomes. (healthymoneyvine.com)
  • Telomerase maintains structures called telomeres, which are composed of repeated segments of DNA found at the ends of chromosomes. (medlineplus.gov)
  • Telomeres protect chromosomes from abnormally sticking together or breaking down (degrading). (medlineplus.gov)
  • Telomerase counteracts the shortening of telomeres by adding small repeated segments of DNA to the ends of chromosomes each time the cell divides. (medlineplus.gov)
  • Telomeres are sequences of DNA on the ends of chromosomes that protect chromosomes from sticking to each other or tangling, which could cause irregularities in normal DNA functions. (asu.edu)
  • As cells replicate, telomeres shorten at the end of chromosomes, which correlates to senescence or cellular aging. (asu.edu)
  • Telomeres are small structures that protect the ends of your chromosomes. (hilfenetzwerk-cic.de)
  • How the ends of chromosomes, called "telomeres", contribute to maintaining DNA health. (cmrijeansforgenes.org.au)
  • For example, recent data suggest that the lengths of telomeres, the DNA sequences at the ends of our chromosomes that shorten with aging, might be associated with COPD. (medlineplus.gov)
  • Telomeres naturally shorten with age. (cdc.gov)
  • Emerging evidence indicates that telomeres shorten with exposure to psychosocial stress (including early-life stress) and perhaps in association with some psychiatric disorders. (nih.gov)
  • However, telomere shortening is also a defense mechanism against cancer because highly proliferative cells can only divide when their telomeres do not shorten. (uni-mainz.de)
  • Individuals are born with telomeres of certain length and in many cells telomeres shorten as the cells divide and age. (nextbigfuture.com)
  • Somatic cells generally do not maintain telomere sequences, and these cells become senescent in adults as telomeres shorten to a critical length. (harvard.edu)
  • So, each time our DNA replicates and our cells divide, our telomeres shorten a little bit. (hackyourgut.com)
  • As our cells divide more and we get older, our telomeres shorten. (hackyourgut.com)
  • Due to the end replication problem, telomeres of somatic cells shorten with each cell division, inducing cell senescence. (imrpress.com)
  • Telomeres shorten each time a cell divides, and when they become too short, cell division stops. (healthymoneyvine.com)
  • But limiting the factors that are negatively associated with telomere length is likely to contribute to a more youthful biological age. (medicalnewstoday.com)
  • European children, particularly those from Finland ( P = 0.041) and from Sweden ( P = 0.001), had shorter telomeres than children from the U.S.A. Paternal age ( P = 0.019) was positively associated with telomere length. (researchsquare.com)
  • For the first time, researchers have found a link between long telomeres and an increased risk for colorectal cancer, according to research presented at the American Association for Cancer Research. (news-medical.net)
  • Researchers have shown that it is possible to extend the life of mice by generating hyper-long telomeres, without using any gene modifying technologies. (news-medical.net)
  • When they discovered that the pattern of cyclic TERRA accumulation was different between short and long telomeres, they knew they were on to something and joined forces for this project. (uni-mainz.de)
  • Their joint work led them to realize that TERRA actually accumulates at all telomeres, but at long telomeres it is rapidly removed with the help of proteins Rat1 and RNase H2. (uni-mainz.de)
  • These proteins bind preferentially to the long telomeres and ensure that TERRA is removed, but they are not present at the critically short telomeres, which means that TERRA remains for a longer time. (uni-mainz.de)
  • The great thing about stem cells is that they express telomerase, so they tend to maintain long telomeres. (hackyourgut.com)
  • Telomere length can be considered as an indicator of an organism's somatic state, long telomeres reflecting higher energy investment in self-maintenance. (elsevier.com)
  • Mice have long telomeres and senesce just fine. (cdc.gov)
  • Shortly after the therapy, the aged cells started dividing and had longer telomeres. (zmescience.com)
  • Thus, sperm telomere length can be used as biomarker for the diagnosis and prognosis of male infertility, since fertile males have longer telomeres and the length decreases with age. (spandidos-publications.com)
  • HLA-DR4/4 or HLA-DR4/X children had significantly longer telomeres compared to children with HLA-DR3/3 or HLA-DR3/9 haplogenotypes ( P = 0.008). (researchsquare.com)
  • In addition, paternal age is positively correlated with longer telomeres 5 . (researchsquare.com)
  • Additionally, cells that are born directly from stem cells likely have longer telomeres than cells that aren't, based on the simple fact that they're one cell division away from exposure to high levels of telomerase. (hackyourgut.com)
  • On one hand, foods including fruits, vegetables, nuts and legumes that contains a high amount of these compounds are associated with longer telomeres. (lifelength.com)
  • These two micronutrients are associated with longer telomeres since they are known to be key compounds for maintenance of DNA stability. (lifelength.com)
  • This, said Dr. Honig, could be because of variations at birth, differences in the rate of telomere attrition during life, environmental influences affecting aging such as diet and exercise, and the presence of other diseases. (medscape.com)
  • Each copy of the minor allele of rs12696304 was associated with an ~75-base-pair reduction in mean telomere length, equivalent to ~3.6 years of age-related telomere-length attrition. (nextbigfuture.com)
  • Importantly, our longitudinal analyses revealed a positive relationship between initial TL and telomere attrition rate within individual lizards, that is lizards with short initial telomeres were subjected to reduced telomere attrition rates compared to lizards with long initial TL. (datadryad.org)
  • Background Telomere attrition is a novel risk element for cardiovascular disease. (exposed-skin-care.net)
  • 2 3 Chronic diseases may accelerate this process leading to premature telomere attrition. (exposed-skin-care.net)
  • Each cell division causes progressive attrition (around 50-200 bp of the telomeres) and is part of determining the lifespan of cells 2 . (researchsquare.com)
  • however, in young children 7 and young adults (around 30 years), telomeres are longer in women than in men, although the attrition rate is higher in women 8 . (researchsquare.com)
  • Thus, during the first 20 years of life, telomere attrition may be accelerated in subjects with HLA-DR4 + 10 . (researchsquare.com)
  • Several mechanisms may contribute to the attrition of telomeres, but there is only one known mechanism in healthy individuals, beyond embryogenesis, that counteracts the shortening of telomeres. (researchsquare.com)
  • In aged primary T cells, mitochondrial stress contributes to telomere attrition measured by a novel imaging flow cytometry assay. (ox.ac.uk)
  • While autophagy has been found to control mitochondrial damage, no link has been made to telomere attrition. (ox.ac.uk)
  • In contrast, mitochondrial stress can contribute to telomere attrition and vice versa. (ox.ac.uk)
  • Biron-Shental T, Wiser A, Hershko-Klement A, Markovitch O, Amiel A and Berkovitch A: Sub-fertile sperm cells exemplify telomere dysfunction. (spandidos-publications.com)
  • Moreover, oxidative stress and aging were considered to be the major causes of inflammation, DNA damage, and telomere dysfunction and shortening [ 2 - 5 ]. (hindawi.com)
  • Critical telomere shortening in the absence of telomerase in late generation Terc -/- mice (G3 Terc -/- ) or loss of telomere capping due to abrogation of the DNA repair/telomere binding protein Ku86 (Ku86 -/- mice) results in telomere dysfunction and organismal premature aging. (elsevier.com)
  • In addition, the data presented in this study support the view that telomere dysfunction induces a robust compensatory response to rescue impaired germ cell function through the induction of survival signals related to the PI3-kinase pathway, as well as by the coordinated upregulation of transcripts that are essential for mammalian spermatogenesis. (elsevier.com)
  • Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease. (ox.ac.uk)
  • Here we assessed the ability of high-resolution single telomere length analysis (STELA), combined with an experimentally derived definition of telomere dysfunction, to predict the clinical outcome of patients with chronic lymphocytic leukaemia (CLL). (ox.ac.uk)
  • In keeping with this finding, telomere dysfunction was the dominant variable in multivariate analysis. (ox.ac.uk)
  • Taken together, this study provides compelling evidence for the use of high-resolution telomere length analysis coupled with a definition of telomere dysfunction in the prognostic assessment of CLL. (ox.ac.uk)
  • Alterations or removal of individual shelterin components would lead to telomere uncapping and telomere dysfunction, resulting in cellular senescence and transformation to a malignant state. (imrpress.com)
  • Telomere shortening, low autophagy and mitochondrial dysfunction have been shown to underpin cell senescence. (ox.ac.uk)
  • Telomerase reactivation following telomere dysfunction yields murine prostate tumors with bone metastases. (bvsalud.org)
  • To determine the role of telomere dysfunction and telomerase reactivation in generating pro-oncogenic genomic events and in carcinoma progression, an inducible telomerase reverse transcriptase (mTert) allele was crossed onto a prostate cancer -prone mouse model null for Pten and p53 tumor suppressors. (bvsalud.org)
  • Constitutive telomerase deficiency and associated telomere dysfunction constrained cancer progression. (bvsalud.org)
  • In contrast, telomerase reactivation in the setting of telomere dysfunction alleviated intratumoral DNA -damage signaling and generated aggressive cancers with rearranged genomes and new tumor biological properties ( bone metastases ). (bvsalud.org)
  • Thus, telomerase reactivation in tumor cells experiencing telomere dysfunction enables full malignant progression and provides a mechanism for acquisition of cancer -relevant genomic events endowing new tumor biological capabilities. (bvsalud.org)
  • July 23, 2012 - Shortening of leukocyte telomeres, the extreme ends of chromosomal DNA, is associated with risks for dementia and mortality, and may be a marker of biological aging, according to a new study. (medscape.com)
  • Socioeconomic status, health behavior, and leukocyte telomere length in the National Health and Nutrition Examination Survey, 1999-2000. (cdc.gov)
  • We conducted genome-wide association analyses of mean leukocyte telomere length in 2,917 individuals, with follow-up replication in 9,492 individuals. (nextbigfuture.com)
  • A previous study indicated that leukocyte telomere length is shortened in AS patients [ 17 ]. (hindawi.com)
  • The aim of this study is to assess baseline mean leukocyte telomere length (TL) as a potential predictive factor for chemotherapy toxicity and a prognostic marker for long-term outcome in early breast cancer (BC) patients. (hilfenetzwerk-cic.de)
  • The results suggest that if telomere length is a determinant of aging, it might be possible to develop agents that prevent telomere shortening, and this might decrease the incidence of age-related dementia, said lead author Lawrence S. Honig, MD, PhD, from the Taub Institute for Research on Alzheimer's Disease and the Aging Brain, and professor of clinical neurology, at Columbia University, New York City. (medscape.com)
  • If telomere shortening is truly an important part of the pathogenetic process of aging and not simply some sort of marker of aging, then we might imagine that intervening in that shortening process might somehow cause people to be biologically younger at a given age. (medscape.com)
  • It appears that telomere shortening may be a necessary biological process in cancer prevention. (medscape.com)
  • So, what if it were possible to treat them by acting on the causes of ageing or, more specifically, by acting on the shortening of telomeres, the structures. (news-medical.net)
  • Researchers have detected a link between alcohol consumption, cancer and aging that starts at the cellular level with telomere shortening. (news-medical.net)
  • The result of this is a progressive shortening of the telomere DNA stretch with every round of cell division. (medicalnewstoday.com)
  • With progressive telomere shortening comes cell senescence. (medicalnewstoday.com)
  • Telomere shortening and changes in the levels of telomerase, the enzyme that maintains telomeres, occur in the context of certain somatic diseases and in response to selected physical stressors. (nih.gov)
  • These discoveries suggest that telomere shortening might be a useful biomarker for the overall stress response of an organism to various pathogenic conditions. (nih.gov)
  • The possibility that telomere shortening can be slowed or reversed by psychiatric and psychosocial interventions could represent an opportunity for developing novel preventative and therapeutic approaches. (nih.gov)
  • Telomere shortening and reduced cell division are considered a hallmark of ageing and likely contribute to the ageing process. (uni-mainz.de)
  • Therefore, telomere shortening is a double-edged sword and has to be carefully regulated to strike a balance between ageing and cancer prevention. (uni-mainz.de)
  • Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study. (greenmedinfo.com)
  • A decreased telomere length has been reported in several diseases and telomere shortening may occur due to aging, decreased telomerase activity, oxidative stress or cell division. (spandidos-publications.com)
  • Sperm telomere shortening is associated with male infertility through several mechanisms, including the apoptosis of spermatozoa, decreased motility, low sperm count, incorrect chromosomal pairing and movement during meiosis, and failed fertilization. (spandidos-publications.com)
  • Several studies reported shortening of sperm telomeres associated with infertility. (spandidos-publications.com)
  • Progressive shortening of telomeres associated with organism ageing leads to ageing. (cnio.es)
  • In the present work, the protective effect of catalpol against AS via inhibiting oxidative stress, DNA damage, and telomere shortening was found in LDLr −/− mice. (hindawi.com)
  • Decrease baseline eGFRCKD-EPI (and all other actions of kidney function) expected more rapid telomere shortening (10.8 [95% CI 4.3-17.3] decrease in base pairs over 5 years for each and every 5 ml/min/1.73 m2 lesser eGFRCKD-EPI). (exposed-skin-care.net)
  • Conclusions In individuals with CHD reduced kidney function is definitely associated with i) shorter baseline telomere size and ii) more rapid telomere shortening over 5 years however these associations are entirely explained by older age. (exposed-skin-care.net)
  • 1] The part of Rivaroxaban telomeres is to prevent chromosome ends from being identified as double strand breaks in DNA thus limiting chromosome shortening and recombination. (exposed-skin-care.net)
  • Clinical studies possess reported that individuals with end-stage renal disease (ESRD) may have shorter telomere size and accelerated telomere shortening compared with the general human population. (exposed-skin-care.net)
  • 8] [9] Within this study we aimed to test the association of six different measures of kidney function with telomere length and telomere shortening over 5 years. (exposed-skin-care.net)
  • On the other hand, a diet that consists of saturated fats, alcohol, sugary drinks and that includes high consumption of processed meat will very likely lead to greater telomere shortening. (lifelength.com)
  • The anti-inflammatory and antioxidant properties, induced by these fatty-acids, can reduce telomere shortening as they decrease the oxidative damage of the DNA. (lifelength.com)
  • Telomere shortening within the CD8+ subset could be prevented in vitro by treatment with a ROS scavenger. (ox.ac.uk)
  • The shortening of human telomeres has two opposing effects during cancer development. (healthymoneyvine.com)
  • On the one hand, telomere shortening can exert a tumour-suppressive effect through the proliferation arrest induced by activating the kinases ATM and ATR at unprotected chromosome ends. (healthymoneyvine.com)
  • v) People with cancer have severe shortening of their telomeres, the protein 'ends' of the DNA strands which keep the DNA strands in place. (canceractive.com)
  • A shortening of telomeres usually signals ageing and a reduced life-span. (canceractive.com)
  • Also, there is shortening of telomere length associated with HIV infection. (aginghiv.org)
  • The p53 gene may have an additional function of signaling cell growth arrest in response to telomere shortening, which occurs with repeated cellular divisions and ultimately threatens chromosomal stability. (elsevier.com)
  • Furthermore, most stem cells are quiescent, and telomere shortening normally only occurs with cell division. (asiatox.org)
  • Telomeres are at the nexus between the two, so understanding how they are maintained is really important', said Brian Luke, Professor at the JGU Institute for Developmental Biology and Neurobiology and Adjunct Director at IMB. (uni-mainz.de)
  • Role of telomerase and telomeres in adult stem cell biology and in nuclear reprogramming of differentiated cells to iPS cells. (cnio.es)
  • Here we study the telomere biology of planarian flatworms with apparently limitless regenerative capacity fueled by a population of highly proliferative adult stem cells. (harvard.edu)
  • With the changing emphasis from genetic to epigenetic understandings of pathology (including telomere biology), with the use of gene delivery systems (including viral delivery systems), and with the use of cell-based therapies (including stem cell therapies), a fatalistic view of age-related disease is no longer a reasonable clinical default nor an appropriate clinical research paradigm. (lidsen.com)
  • Precedence will be given to papers describing fundamental interventions, including interventions that affect cell senescence, patterns of gene expression, telomere biology, stem cell biology, and other innovative, 21st century interventions, especially if the focus is on clinical applications, ongoing clinical trials, or animal trials preparatory to phase 1 human clinical trials. (lidsen.com)
  • Thus, it is important to understand the telomere biology so as to deal with normal physiologic processes such as apoptosis, aging and senescence and tumor development. (healthymoneyvine.com)
  • Our studies of telomere biology and DNA replication led us unexpectedly to identify how lethal replication stress induces cell death specifically during mitosis through a pathway of cohesion fatigue and non-canonical telomere deprotection. (cmrijeansforgenes.org.au)
  • Following this, she then served from 2008-2011 in a postdoctoral training in telomere biology and single-molecule imaging at the University of Pittsburgh. (ncsu.edu)
  • Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. (medscape.com)
  • In this process, the telomere itself shortens with each cell division and can consequently be thought of as a cellular 'clock', reflecting the age of a cell and the time until senescence. (nih.gov)
  • We already knew that short telomeres play a key role in determining the onset of cellular senescence, but we didn't really understand which features of short telomeres were important. (uni-mainz.de)
  • Telomere length is closely associated with cell senescence [ 12 - 14 ]. (hindawi.com)
  • Moreover, it is found that mitochondria and telomere link contributes to the induction of cancer cell senescence and PGC-1 α is the key molecule to link oxidative stress and telomere function [ 19 ]. (hindawi.com)
  • With natural ageing DNA polymerase is not able to fully replicate the 3′ end of linear DNA resulting Rivaroxaban in an obligate and progressive loss of telomere repeats with each cell division - eventually resulting in cellular senescence or apoptosis. (exposed-skin-care.net)
  • Telomere length (TL) has been associated with cellular longevity and is thought to play an important role in cellular aging and senescence. (2minutemedicine.com)
  • Telomerase activity is necessary for the stabilization of telomeres, which function to overcome cellular senescence and are linked to unlimited cell proliferation. (elsevier.com)
  • This ability plays a key role in lengthening and maintaining telomeres, as HTTs typically get inserted at chromosome-ends ( Casacuberta, 2017 ), but they can also cause genome instability if these sequences replicate without control. (elifesciences.org)
  • Telomeres prevent the loss of coding sequences and hinder major chromosomal rearrangements 1 . (researchsquare.com)
  • Some cell types, such as lymphocytes, are capable of activating telomerase, an enzyme that can elongate telomere sequences and thereby modulate cellular lifespan. (researchsquare.com)
  • In most sexually reproducing animals, replication and maintenance of telomeres occurs in the germ line and during early development in embryogenesis through the use of telomerase. (harvard.edu)
  • Telomerase reverse transcriptase (TERT), the protein subunit of telomerase, maintains telomere ends during DNA replication by catalyzing the addition of short telomere repeats [ 15 ]. (hindawi.com)
  • In addition to this role, telomeres function to protect the ends of DNA during the process of DNA replication. (hackyourgut.com)
  • Fortunately, there's an enzyme called telomerase that can re-lengthen telomeres that are shortened during DNA replication. (hackyourgut.com)
  • Alternative lengthening of telomeres (ALT) cancers achieve immortality by reelongating their telomeres in the G2 and M phases of the cell cycle through a specialized break-induced replication (BIR) pathway (1, 2). (hilfenetzwerk-cic.de)
  • We identified that telomere-loops (t-loops) function specifically to regulate ATM activity at human and mouse telomeres and collaborated with the Boulton Lab from the Crick Institute to identify how t-loops are resolved during S-phase to enable telomere replication. (cmrijeansforgenes.org.au)
  • 2020. Structurally distinct telomere-binding proteins in Ustilago maydis execute non-overlapping functions in telomere replication, recombination, and protection. . (cornell.edu)
  • Her research focuses on single-molecule experimental investigations of the structure-function relationships that govern the maintenance of telomeres. (ncsu.edu)
  • The variants identified lies near a gene called TERC which is already known to play an important role in maintaining telomere length. (nextbigfuture.com)
  • Sep 22, 2022 Telomere vesicles retained the Rad51 recombination factor that enabled telomere fusion with T-cell chromosome ends lengthening them by an average of 3,000 base pairs. (hilfenetzwerk-cic.de)
  • On the other hand, loss of telomere protection can lead to telomere crisis, which is a state of extensive genome instability that can promote cancer progression. (healthymoneyvine.com)
  • In addition, the DNA in Drosophila telomeres is wrapped around proteins decorated with a specific mark recognized by Heterochromatin Protein 1 (HP1 for short) to ensure that they remain in their compacted form. (elifesciences.org)
  • Given the critical role of telomeres, it is intriguing that flies have evolved a protective mechanism that involves parasitic elements and factors like HOAP and HipHop, which are two of the fastest evolving proteins in Drosophila ( Saint-Leandre and Levine, 2020 ). (elifesciences.org)
  • Telomeres are essentially made out of the same building blocks as DNA, but they don't actually contain blueprint information that's translated in to the proteins that make you. (hackyourgut.com)
  • Human telomeres are associated with the shelterin complex which consists of six telomere-associated proteins that specifically bind to telomeric DNA. (imrpress.com)
  • Another complex of multifunctional proteins, named non-shelterin complex, is thought to prevent telomere degradation and facilitate telomerase-based telomere elongation. (imrpress.com)
  • In this review, we will summarize the characteristics of telomeres and telomerase in lymphoid malignancies and discuss the role of telomere-associated proteins in these entities. (imrpress.com)
  • It takes two crews of proteins to keep the telomeres in fine fettle, as Kim et al. (rupress.org)
  • TRF1 and TRF2 are just two of the proteins that ensure that a cell's telomeres remain long and structurally sound. (rupress.org)
  • Another protein, TIN2, links up with both molecules and with other proteins to form complexes that help maintain the telomeres. (rupress.org)
  • 2015. Telomere DNA recognition in Saccharomycotina yeast: potential lessons for the co-evolution of ssDNA and dsDNA-binding proteins and their target sites. . (cornell.edu)
  • The goal of her current research is to use two highly innovative and complementary single-molecule imaging techniques (atomic force microscopy and fluorescence imaging) together with quantum dot labeled proteins to investigate the effects of DNA damage on the conformational and dynamic properties of telomeric DNA structure and telomere binding proteins. (ncsu.edu)
  • Likewise, a systematic review published in the September 2017 issue of the Journal of Psychiatric Research also shows an association between adversity during childhood - including violence, institutionalization, and poverty - and shorter telomeres. (medicalnewstoday.com)
  • Vitamin D - A scientific article published in 2017 in the "Journal of Nutrition" concluded that those individuals with low Vitamin D had shorter telomeres than those whose levels were adequate. (lifelength.com)
  • Research Gate dated January 2017 published this telomeres information article " Telomeres in cancer: Tumour suppression and genome instability . (healthymoneyvine.com)
  • 2017. Telomere recombination pathways: tales of several unhappy marriages. . (cornell.edu)
  • This mechanism ensures the subsequent repair of the short telomere, which is crucial for the cell to survive and keep dividing. (uni-mainz.de)
  • Short telomere length is a predictor of heart disease, aging and cancer. (healthymoneyvine.com)
  • In healthy subjects, HLA-DRB1*04 alleles have been shown to be associated with shorter telomeres in CD4 + T-cells, although the difference in telomere length between HLA-DR4 + and HLA-DR4 − subjects was not identified at birth. (researchsquare.com)
  • This difference in telomere length coupled with the more rapid rate of cell division in cancer cells makes the inhibition of telomerase a stylish potential breast cancer therapeutic target. (asiatox.org)
  • Cancer researchers are studying the impact of telomere loss on cancer risk. (medscape.com)
  • We identified an association with telomere length on 3q26 (rs12696304, combined P = 3.72 × 10−14) at a locus that includes TERC, which encodes the telomerase RNA component. (nextbigfuture.com)
  • Telomere length (TL) is likely influenced by genetic factors, as well as by factors such as smoking, diet, and physical activity, the researchers write. (medscape.com)
  • Scientists discovered that having children significantly shortened telomeres (genetic markers of aging). (zmescience.com)
  • In this study what we found was that those individuals carrying a particular genetic variant had shorter telomeres i.e. looked biologically older. (nextbigfuture.com)
  • The telomeres in flies carrying the D. yakuba variant did not have the genetic marks recognized by HP1 and recruited much less of this protein. (elifesciences.org)
  • These telomeres are responsible for protecting the genetic data. (healthymoneyvine.com)
  • Dr. Jay Sarthy is a hematologist-oncologist who specializes in pediatric bone marrow transplantation for children with blood cancers and rare genetic conditions, such as telomere syndromes. (seattlechildrens.org)
  • Genetic mutations and telomere length may influence the course of the ILD and be associated with a worse prognosis. (medscape.com)
  • Special structures called telomeres keep a close eye on the damage that accumulates in our cells and signal when it is time for them to retire. (medicalnewstoday.com)
  • The telomere capping complex CST has an unusual stoichiometry, makes multipartite interaction with G-Tails, and unfolds higher-order G-tail structures. (cornell.edu)
  • Researchers, journalists, and inquiring minds want to know more about telomeres, which seem to hold clues to human aging and age-related diseases. (cdc.gov)
  • Alternatively genetically susceptible people may age even faster when exposed to proven 'bad' environments for telomeres like smoking, obesity or lack of exercise - and end up several years biologically older or succumbing to more age-related diseases. (nextbigfuture.com)
  • Telomere length is an important biomarker in a number of diseases, including male infertility. (spandidos-publications.com)
  • Generating mouse models to validate telomeres and telomerase as therapeutic targets for cancer and age-related diseases. (cnio.es)
  • Testing telomerase gene therapy in telomere syndromes and age-related diseases. (cnio.es)
  • Telomere length exhibits disease-specific patterns in different autoimmune diseases 2 , 14 , 15 . (researchsquare.com)
  • In this current study, we examined cross-sectional associations among social-demographics, lifestyle behaviors, and relative telomere length (RTL) in peripheral blood leukocytes, as well as longitudinal relationships among major chronic diseases, weight gain, and RTL, among 12,792 Mexican Americans aged 20 to 85 years in the Mano-A-Mano, a Mexican American Cohort. (tmc.edu)
  • Research suggests that control of the telomere length has the potential to treat many diseases linked to aging. (lisatamati.com)
  • 2018. Single telomere length analysis in Ustilago maydis, a high-resolution tool for examining fungal telomere length distribution and C-strand 5'-end processing. . (cornell.edu)
  • In this regard, telomeres and their response to both somatic and psychiatric illness could serve as a unifying stress-response biomarker that crosses the brain/body distinction that is often made in medicine. (nih.gov)
  • Keywords: kidney CKD telomere Intro Telomere size is a novel biomarker of physiologic age and cardiovascular risk. (exposed-skin-care.net)
  • We already know that the telomere length is a key biomarker of our tissue renewal capacity and therefore an important indicator of our aging process. (lifelength.com)
  • We shall also request access to physiological biomarker, biological age (telomere length) and polygenic risk score (26211) data (for asthma). (ukbiobank.ac.uk)
  • Objective -To measure telomere length and telomerase activity in naturally occurring canine mammary gland tumors. (avma.org)
  • Adults with post-traumatic stress disorder and a history of childhood trauma had significantly shorter telomere length than those with PTSD but without childhood trauma, in a study by researchers at. (news-medical.net)
  • Shorter telomere length in leukocytes has been reported in subjects with type 1 diabetes (T1D) compared to controls, although shorter telomere length was not associated with the duration of T1D 16 . (researchsquare.com)
  • Relative telomere length (RTL) was measured using quantitative real-time PCR. (greenmedinfo.com)
  • Relative telomere length (RTL), parameters of retinal microvascular function, CVD circulatory markers and blood pressure (BP) were measured in all individuals. (aston.ac.uk)
  • Our novel assay is a sensitive assay to measure relative telomere length in primary cells and has revealed ROS as a contributing factor to the decline in telomere length. (ox.ac.uk)
  • BOTTOM LINE Telomere length decreases with age. (aginghiv.org)
  • Mutations affecting telomere or any component of telomerase enzyme result in disorders such as dyskeratosis congenita, aplastic anemia, myelodysplastic syndromes and leukemias. (healthymoneyvine.com)
  • During the "in vivo" reprogramming process, cellular telomeres are extended due to an increase in endogenous telomerase. (bioquicknews.com)
  • We have found that when you induce cell de-differentiation in an adult organism, the telomeres become longer, which is consistent with cellular rejuvenation," explains Dr. María A. Blasco, head of the CNIO Telomeres and Telomerase Group and leader of this research. (bioquicknews.com)
  • The role of prenatal environmental pollution exposure on neonatal telomere length and its predisposition to cellular aging is unknown. (2minutemedicine.com)
  • Telomeres help in maintaining the cellular health, inbuilt cellular mechanisms, metabolism and normal cell cycle. (healthymoneyvine.com)
  • Alterations in telomere length are indicative of cellular aging and, possibly, neurodegeneration. (cdc.gov)
  • HOAP is a telomere-binding protein that has a conserved role in Drosophila , but it also needs to evolve quickly to restrict telomeric retrotransposons. (elifesciences.org)
  • Telomeres are a protective nucleoprotein structure at each chromosome end. (cdc.gov)
  • We show that somatic telomere maintenance is different in asexual and sexual animals. (harvard.edu)
  • The adaptations we observe demonstrate indefinite somatic telomerase activity in proliferating stem cells during regeneration or reproduction by fission, and establish planarians as a pertinent model for studying telomere structure, function, and maintenance. (harvard.edu)
  • Early-life is a period of intense investment in somatic growth and in physiological maturation but how this is reflected in telomere length remains unclear. (elsevier.com)
  • Depending on environmental conditions, our data suggest links between somatic growth, physiological maturation and body maintenance parameters (positive with oxidative stress and negative with telomere length) in nestlings. (elsevier.com)
  • It allows one to come up with mostly reproducible and more informative numbers as to the average telomere repeat length. (medscape.com)
  • Telomerase inhibition as an anticancer approach The average telomere length in breast cancer cells is usually well below that of normal cells. (asiatox.org)
  • Patients with severe COVID-19 disease have significantly shorter telomeres, according to a study conducted by researchers at the Spanish National Cancer Research Centre in collaboration with the. (news-medical.net)
  • For example, a recent study published in the journal Pediatrics demonstrates that children who had lost their fathers had significantly shorter telomeres. (medicalnewstoday.com)
  • Telomeres in mammary gland tumors were slightly shorter than in normal tissue specimens, but telomere length could not be directly compared between groups, because mean age of dogs was significantly different between groups. (avma.org)
  • Age was negatively correlated with telomere length in control dogs but was not significantly correlated with length in affected dogs. (avma.org)
  • Estimated telomere length was not significantly different with respect to any IA ( P = 0.377), IAA-first ( P = 0.248), GADA-first ( P = 0.248) or T1D ( P = 0.861). (researchsquare.com)
  • Results Telomeres length of T helper, T cytotoxic, natural killer and B cells increased significantly by over 20 following HBOT. (hilfenetzwerk-cic.de)
  • Telomeres shortened significantly over the 21 days between the baseline and final sample, independent of sex, mass, size and hatching order. (hilfenetzwerk-cic.de)
  • While comparisons across studies of telomere length in base pairs are commonly done, it is not highly accurate. (cdc.gov)
  • These results suggest that telomere length has no major impact on the risk for IA, the first step to develop T1D. (researchsquare.com)
  • When telomeres are altered, adult stem cells have a maimed regenerative capacity. (cnio.es)
  • Asexual adult planarian stem cells appear to maintain telomere length over evolutionary timescales without passage through a germ-line stage. (harvard.edu)
  • Upregulation of PGC-1 α in aortic smooth muscle cells can enhance the telomere function and reduce DNA damage to inhibit AS [ 5 ]. (hindawi.com)
  • As traditional methods for measuring telomere length are low throughput or unsuitable for the analysis of cell subtypes within a mixed population of primary cells, we have developed a novel sensitive flow-FISH assay using the imaging flow cytometer. (ox.ac.uk)
  • The current study found that prenatal environmental pollution exposure was linked to decreased telomere length measured in cord blood and placental cells. (2minutemedicine.com)
  • An increase of 5 μg/m3 increment in PM 2.5 exposure was associated with 8.8% (95%CI, −14.1%to −3.1%) and 13.2% (95%CI, −19.3%to −6.7%) decreased telomere length in cord blood and placental cells respectively. (2minutemedicine.com)
  • In most cells, telomeres become progressively shorter as the cell divides. (medlineplus.gov)
  • Mutations in the TERC gene reduce or eliminate the function of telomerase, which allows telomeres to become abnormally short as cells divide. (medlineplus.gov)
  • The shortened telomeres likely trigger cells that divide rapidly, such as cells that line the inside of the lungs, to stop dividing or to die prematurely. (medlineplus.gov)
  • Cells that divide rapidly are especially vulnerable to the effects of shortened telomeres. (medlineplus.gov)
  • Integral to this process is telomerase, which is an enzyme that repairs telomeres and is present in various cells in the human body, especially during human growth and development. (asu.edu)
  • Previous studies have shown that around 85 of cancer cells upregulate the telomerase enzyme through a different mechanism to lengthen telomeres. (hilfenetzwerk-cic.de)
  • Thus, there are antigen -specific populations of T cells whose ageing fate decisions are based on telomere vesicle transfer upon initial contact with APCs. (hilfenetzwerk-cic.de)
  • This prompted us to consider whether the enzyme telomerase, responsible for adding new telomeres to chromosomal ends, may be affected by the p53 status of normal and malignant cells. (elsevier.com)
  • While normal, proliferating telomerase-positive stem cells may also initially be affected, their telomeres are well above the critically short length that induces a DNA damage/growth arrest mechanism. (asiatox.org)
  • Since most breast cancer cells have very short telomeres, treatment with telomerase inhibitors should lead to growth arrest and cell death. (asiatox.org)
  • We age because our telomeres get shorter and our cells age. (lisatamati.com)
  • Every time our cells divide, our telomeres get shorter and our cells age. (lisatamati.com)
  • The DNA Reprogramming recodes the original Divine eight-cell blueprint with the 5D affirmations given for each chakra, as well as capping the two strand DNA with telomere, a protein-like substance that will hold this new belief permanently within the original Divine eight-cells. (acoustichealth.com)
  • Asexual animals maintain telomere length somatically during reproduction by fission or when regeneration is induced by amputation, whereas sexual animals only achieve telomere elongation through sexual reproduction. (harvard.edu)
  • Marilyn Vine brings you telomeres information on how to lengthen them to aid in longevity. (healthymoneyvine.com)
  • More than 2,500 tumour genomes of 36 types of cancer were analysed and the team found DNA mutations pointing to one of the two known mechanisms to lengthen telomeres in 13 of the cases . (hilfenetzwerk-cic.de)
  • Dysfunctional telomeres are important contributing factors in aging and tumorigenesis. (ncsu.edu)
  • Dysfunctional telomeres and dyskeratosis congenita. (medscape.com)
  • Mason PJ, Wilson DB, Bessler M. Dyskeratosis congenita -- a disease of dysfunctional telomere maintenance. (medscape.com)
  • 2010. Rap1 in Candida albicans: an unusual structural organization and a critical function in suppressing telomere recombination. . (cornell.edu)
  • These findings suggest a possible correlation between epigenetic modifications, telomere length alteration, and neurodegeneration because of the presence of factors in serum after WF exposure that may cause extra-pulmonary effects as well as the translocation of potentially neurotoxic metals associated with WF to the central nervous system (CNS). (cdc.gov)
  • Over a cell's lifetime, telomeres get gradually shorter with each cell division and therefore the protective cap becomes less and less effective. (uni-mainz.de)
  • This study also shows that activation of the peroxisome proliferator-activated receptor- γ coactivator-1 α (PGC-1 α )/telomerase reverse transcriptase (TERT) pathway, which is the new link between mitochondria and telomere, was involved in the protective effects of catalpol. (hindawi.com)
  • A secret, affecting telomeres--the protective tip of the human chromosome that controls cell life. (bublish.com)
  • PDF file related to telomere lengthening in humans, and natural product telomerase activators, written by Phillip A Micans, MS, PharmB 44-208-123-2106 iasantiaging-systems.com Menu . (hilfenetzwerk-cic.de)
  • Telomere length can be used to indicate an individual's biological age (which is different from chronological age). (medicalnewstoday.com)
  • With a team of researchers from China and Saudi Arabia, Koenig studied the telomere lengths of Chinese Muslims which are key indicators of age and well-being. (thefederalist.com)
  • Reverse transcriptase at bacterial telomeres. (cornell.edu)
  • Further, by using PGC-1 α or TERT siRNA in oxLDL-treated macrophages, it is proved that catalpol reduced oxidative stress, telomere function, and related DNA damage at least partly through activating the PGC-1 α /TERT pathway. (hindawi.com)